INPP4B

Summary

Gene Symbol: INPP4B
Description: inositol polyphosphate-4-phosphatase type II B
Alias: type II inositol 3,4-bisphosphate 4-phosphatase, inositol polyphosphate 4-phosphatase II; 4-phosphatase II, inositol polyphosphate-4-phosphatase, type II, 105kDa
Species: human
Products:     INPP4B

Top Publications

  1. Norris F, Atkins R, Majerus P. The cDNA cloning and characterization of inositol polyphosphate 4-phosphatase type II. Evidence for conserved alternative splicing in the 4-phosphatase family. J Biol Chem. 1997;272:23859-64 pubmed
    ..coli and SF9 insect cells and found to possess no detectable enzymatic activity suggesting that additional factors and/or processing may be required for these alternatively spliced isozymes. ..
  2. Norris F, Auethavekiat V, Majerus P. The isolation and characterization of cDNA encoding human and rat brain inositol polyphosphate 4-phosphatase. J Biol Chem. 1995;270:16128-33 pubmed
    ..This antiserum also immunoprecipitated the 4-phosphatase from human platelet sonicates. ..
  3. Perez Lorenzo R, Gill K, Shen C, Zhao F, Zheng B, Schulze H, et al. A tumor suppressor function for the lipid phosphatase INPP4B in melanocytic neoplasms. J Invest Dermatol. 2014;134:1359-1368 pubmed publisher
    ..Recently, a tumor suppressor function for the lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described in breast and prostate cancers, with impact on PI3K signaling output...
  4. Agoulnik I, Hodgson M, Bowden W, Ittmann M. INPP4B: the new kid on the PI3K block. Oncotarget. 2011;2:321-8 pubmed
    ..Recently, another lipid phosphatase, Inositol Polyphosphate 4-phosphatase type II (INPP4B), has emerged as a potential tumor suppressor in prostate, breast, and ovarian cancers and possibly in leukemia...
  5. Gewinner C, Wang Z, Richardson A, Teruya Feldstein J, Etemadmoghadam D, Bowtell D, et al. Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell. 2009;16:115-25 pubmed publisher
    We report that knocking down the expression of inositol polyphosphate 4-phosphatase type II (INPP4B) in human epithelial cells, like knockdown of PTEN, resulted in enhanced Akt activation and anchorage-independent growth and enhanced ..
  6. Fedele C, Ooms L, Ho M, Vieusseux J, O Toole S, Millar E, et al. Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers. Proc Natl Acad Sci U S A. 2010;107:22231-6 pubmed publisher
    Inositol polyphosphate 4-phosphatase-II (INPP4B) is a regulator of the phosphoinositide 3-kinase (PI3K) signaling pathway and is implicated as a tumor suppressor in epithelial carcinomas...
  7. Zhang F, Li J, Zhu J, Liu L, Zhu K, Cheng S, et al. IRF2-INPP4B-mediated autophagy suppresses apoptosis in acute myeloid leukemia cells. Biol Res. 2019;52:11 pubmed publisher
    ..the underlying role of interferon-regulatory factor 2 (IRF2)-inositol polyphosphate-4-phosphatase, type-II (INPP4B) axis in the regulation of autophagy in acute myeloid leukemia (AML) cells...
  8. Liang X, Briaux A, Becette V, Benoist C, Boulai A, Chemlali W, et al. Molecular profiling of hormone receptor-positive, HER2-negative breast cancers from patients treated with neoadjuvant endocrine therapy in the CARMINA 02 trial (UCBG-0609). J Hematol Oncol. 2018;11:124 pubmed publisher
    ..3%), CDH1 (20.2%), PTEN (15.7%), TP53 (10.1%), LAMA2 (10.1%), BRCA2 (9.0%), MAP3K1 (7.9%), ALK (6.7%), INPP4B (6.7%), NCOR1 (6.7%), and NF1 (5.6%)...
  9. Vo T, Fruman D. INPP4B Is a Tumor Suppressor in the Context of PTEN Deficiency. Cancer Discov. 2015;5:697-700 pubmed publisher
    ..In this issue of Cancer Discovery, Kofuji and colleagues and Chew and colleagues identify the lipid phosphatase INPP4B as a context-specific tumor suppressor that controls phosphoinositide levels and AKT2 activation in PTEN-deficient ..

More Information

Publications79

  1. Zhang M, Suarez E, Vasquez J, Nathanson L, Peterson L, Rajapakshe K, et al. Inositol polyphosphate 4-phosphatase type II regulation of androgen receptor activity. Oncogene. 2019;38:1121-1135 pubmed publisher
    ..reprogramming of AR in advanced prostate cancer frequently coincides with the loss of two tumor suppressors, INPP4B and PTEN, which are highly expressed in human and mouse prostate epithelium...
  2. Xu H, Sun H, Zhang H, Liu J, Fan F, Li Y, et al. An ShRNA Based Genetic Screen Identified Sesn2 as a Potential Tumor Suppressor in Lung Cancer via Suppression of Akt-mTOR-p70S6K Signaling. PLoS ONE. 2015;10:e0124033 pubmed publisher
    ..A total of 6 candidate transformation suppressors including INPP4B, Sesn2, TIAR, ACRC, Nup210, LMTK3 were identified...
  3. Li X, Edwards M, Swaney K, Singh N, Bhattacharya S, Borleis J, et al. Mutually inhibitory Ras-PI(3,4)P2 feedback loops mediate cell migration. Proc Natl Acad Sci U S A. 2018;115:E9125-E9134 pubmed publisher
    ..depletion of PI(3,4)P2 by disruption of the 5-phosphatase, Dd5P4, or by recruitment of 4-phosphatase INPP4B to the plasma membrane, leads to elevated Ras activity, cell spreading, and altered migratory behavior...
  4. Marchiò C, De Filippo M, Ng C, Piscuoglio S, Soslow R, Reis Filho J, et al. PIKing the type and pattern of PI3K pathway mutations in endometrioid endometrial carcinomas. Gynecol Oncol. 2015;137:321-8 pubmed publisher
    ..used to define the number, type and pattern of mutations affecting PI3K pathway-related genes, including AKT1, INPP4B, MTOR, PIK3CA, PIK3R1 and PTEN...
  5. Ndila C, Uyoga S, Macharia A, Nyutu G, Peshu N, Ojal J, et al. Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study. Lancet Haematol. 2018;5:e333-e345 pubmed publisher
    ..in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS...
  6. Manzano R, Martínez Navarro E, Forteza J, Brugarolas A. Microarray phosphatome profiling of breast cancer patients unveils a complex phosphatase regulatory role of the MAPK and PI3K pathways in estrogen receptor-negative breast cancers. Int J Oncol. 2014;45:2250-66 pubmed publisher
    ..expressed phosphatases (like DUSP4 and DUSP6) sharing ERK as substrate, or regulating the PI3K pathway (INPP4B, PTEN)...
  7. Tanioka M, Sakai K, Sudo T, Sakuma T, Kajimoto K, Hirokaga K, et al. Transcriptional CCND1 expression as a predictor of poor response to neoadjuvant chemotherapy with trastuzumab in HER2-positive/ER-positive breast cancer. Breast Cancer Res Treat. 2014;147:513-25 pubmed publisher
    ..In a univariate analysis, a pCR was associated with high mRNA levels of ESR1, PGR, LMTK3, HER2, IGF1R, INPP4B, PDL-1, BCL-2, and CCND1 (P ≤ 0.05)...
  8. Sowalsky A, Xia Z, Wang L, Zhao H, Chen S, Bubley G, et al. Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer. Mol Cancer Res. 2015;13:98-106 pubmed publisher
    ..found in a series of genes with prostate cancer relevance, including AR, NCOR1, KDM3A, KDM4A, CHD1, SETD5, SETD7, INPP4B, RASGRP3, RASA1, TP53BP1, and CDH1, and a novel SND1:BRAF gene fusion...
  9. Nunes M, Vrignaud P, Vacher S, Richon S, Lièvre A, Cacheux W, et al. Evaluating patient-derived colorectal cancer xenografts as preclinical models by comparison with patient clinical data. Cancer Res. 2015;75:1560-6 pubmed publisher
    ..We found frequent IGF2 upregulation (16%), which was mutually exclusive with IRS2, PIK3CA, PTEN, and INPP4B alterations, supporting IGF2 as a potential drug target...
  10. Spinelli L, Lindsay Y, Leslie N. PTEN inhibitors: an evaluation of current compounds. Adv Biol Regul. 2015;57:102-11 pubmed publisher
    ..of only 3 other related enzymes, the tyrosine phosphatase SHP1 and the phosphoinositide phosphatases INPP4A and INPP4B. Even with this very small number of comparators, for all compounds, inhibition of multiple enzymes was observed ..
  11. Jin H, Yang L, Wang L, Yang Z, Zhan Q, Tao Y, et al. INPP4B promotes cell survival via SGK3 activation in NPM1-mutated leukemia. J Exp Clin Cancer Res. 2018;37:8 pubmed publisher
    ..Inositol polyphosphate 4-phosphatase type II (INPP4B), a new factor in the phosphoinositide-3 kinase (PI3K) pathway-associated cancers, has been recently found a ..
  12. Hawkins P, Stephens L. Emerging evidence of signalling roles for PI(3,4)P2 in Class I and II PI3K-regulated pathways. Biochem Soc Trans. 2016;44:307-14 pubmed publisher
    ..Further, its inappropriate accumulation contributes to pathology caused by mutations in genes encoding enzymes responsible for its degradation, e.g. Inpp4B.
  13. Ji L, Kim N, Huh S, Rhee H. Depletion of Inositol Polyphosphate 4-Phosphatase II Suppresses Callosal Axon Formation in the Developing Mice. Mol Cells. 2016;39:501-7 pubmed publisher
    ..Here, we provide the first report on the role of inositol polyphosphate 4-phosphatase II (INPP4B), a PI(3,4)P2 metabolizing 4-phosphatase in the regulation of callosal axon formation...
  14. Guerini Rocco E, Piscuoglio S, Ng C, Geyer F, De Filippo M, Eberle C, et al. Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations. J Pathol. 2016;238:677-88 pubmed publisher
    ..with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified...
  15. Xie B, He X, Hua R, Zhang B, Tan G, Xiong S, et al. Mir-765 promotes cell proliferation by downregulating INPP4B expression in human hepatocellular carcinoma. Cancer Biomark. 2016;16:405-13 pubmed publisher
    ..Furthermore, we demonstrated that INPP4B as a direct target of mir-765 and ectopic expression of mir-765 repressed INPP4B expression, resulting in ..
  16. Geyer F, Berman S, Marchio C, Burke K, Guerini Rocco E, Piscuoglio S, et al. Genetic analysis of microglandular adenosis and acinic cell carcinomas of the breast provides evidence for the existence of a low-grade triple-negative breast neoplasia family. Mod Pathol. 2017;30:69-84 pubmed publisher
    ..Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA, and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those ..
  17. She Q, Gruvberger Saal S, Maurer M, Chen Y, Jumppanen M, Su T, et al. Integrated molecular pathway analysis informs a synergistic combination therapy targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer. BMC Cancer. 2016;16:587 pubmed publisher
    ..Sixty-four % of cases had an oncogenic alteration to PIK3CA, PTEN, or INPP4B; when including upstream kinases HER2 and EGFR, 75 % of cases had one or more aberration including 97 % of ..
  18. Chen Y, Sun Z, Qi M, Wang X, Zhang W, Chen C, et al. INPP4B restrains cell proliferation and metastasis via regulation of the PI3K/AKT/SGK pathway. J Cell Mol Med. 2018;22:2935-2943 pubmed publisher
    ..Inositol polyphosphate 4-phosphatase type II (INPP4B) is a phosphoinositide phosphatase and considered a negative regulatory factor of the PI3K/AKT pathway...
  19. Dey N, Krie A, Klein J, Williams K, McMillan A, Elsey R, et al. Down's Syndrome and Triple Negative Breast Cancer: A Rare Occurrence of Distinctive Clinical Relationship. Int J Mol Sci. 2017;18: pubmed publisher
    ..The CGP report showed a frameshift mutation, A359fs*10 of the tumor suppressor gene INPP4B and another frameshift mutation, R282fs*63 of tumor suppressor gene TP53 in the tumor biopsy as ..
  20. Li H, Marshall A. Phosphatidylinositol (3,4) bisphosphate-specific phosphatases and effector proteins: A distinct branch of PI3K signaling. Cell Signal. 2015;27:1789-98 pubmed publisher
    ..Signaling through PI(3,4)P2 can be negatively regulated by inositol polyphosphate 4-phosphatases (INPP4A and INPP4B), which selectively degrade PI(3,4)P2...
  21. Hatem R, El Botty R, Chateau Joubert S, Servely J, Labiod D, de Plater L, et al. Targeting mTOR pathway inhibits tumor growth in different molecular subtypes of triple-negative breast cancers. Oncotarget. 2016;7:48206-48219 pubmed publisher
    ..Expression of the tumor suppressors PTEN and INPP4B was lost in 55% and 76% of TNBC PDX, respectively, while mutations in PIK3CA and AKT1 genes were rare...
  22. Showler K, Nishimura M, Daino K, Imaoka T, Nishimura Y, Morioka T, et al. Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas. J Radiat Res. 2017;58:183-194 pubmed publisher
    ..The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced ..
  23. Rodgers S, Ferguson D, Mitchell C, Ooms L. Regulation of PI3K effector signalling in cancer by the phosphoinositide phosphatases. Biosci Rep. 2017;37: pubmed publisher
    ..inositol polyphosphate 5-phosphatase (PIPP) (INPP5J) and inositol polyphosphate 4-phosphatase type II (INPP4B)...
  24. Woolley J, Dzneladze I, Salmena L. Phosphoinositide signaling in cancer: INPP4B Akt(s) out. Trends Mol Med. 2015;21:530-2 pubmed publisher
    b>INPP4B acts as a tumor suppressor in various epithelial cancers by inhibiting PI3K/Akt signaling. Unexpectedly, tumor-promoting features of INPP4B in leukemia and breast cancer have been recently uncovered...
  25. Hodgson M, Deryugina E, Suarez E, Lopez S, Lin D, Xue H, et al. INPP4B suppresses prostate cancer cell invasion. Cell Commun Signal. 2014;12:61 pubmed publisher
    b>INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease...
  26. Yuen J, Chung G, Lun S, Cheung C, To K, Lo K. Epigenetic inactivation of inositol polyphosphate 4-phosphatase B (INPP4B), a regulator of PI3K/AKT signaling pathway in EBV-associated nasopharyngeal carcinoma. PLoS ONE. 2014;9:e105163 pubmed publisher
    ..Aside from the previously reported PIK3CA amplification, we examined the role of INPP4B, a negative regulator of the PI3K/AKT signaling pathway in the development of NPC...
  27. Maekawa M, Terasaka S, Mochizuki Y, Kawai K, Ikeda Y, Araki N, et al. Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis. Proc Natl Acad Sci U S A. 2014;111:E978-87 pubmed publisher
    ..b>INPP4B, which dephosphorylates PI(3,4)P2 to PI(3)P, was also found to be essential for macropinocytosis...
  28. Salmena L, Shaw P, Fans I, McLaughlin -, Rosen B, Risch H, et al. Prognostic value of INPP4B protein immunohistochemistry in ovarian cancer. Eur J Gynaecol Oncol. 2015;36:260-7 pubmed
    ..The impact of altered INPP4B protein expression on prognosis is unclear...
  29. Sung J, Na K, Kim H. Down-regulation of Inositol Polyphosphate 4-Phosphatase Type II Expression in Colorectal Carcinoma. Anticancer Res. 2017;37:5525-5531 pubmed
    ..Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and has a tumor-suppressive role in several human ..
  30. Clarke C, Lee M, Wei W, Manyam G, Jiang Z, Lu Y, et al. Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival. Ann Surg Oncol. 2017;24:4051-4058 pubmed publisher
    ..were found to be significant predictors of tumor recurrence on multivariate analysis: Collagen VI, FOXO3a, INPP4B, LcK, phospho-PEA15, phospho-PRAS40, Rad51, phospho-S6...
  31. Vacher J. [Inositol phosphatase and bone mass: role of INPP4b]. Med Sci (Paris). 2012;28:152-3 pubmed publisher
  32. Dai X, Fagerholm R, Khan S, Blomqvist C, Nevanlinna H. INPP4B and RAD50 have an interactive effect on survival after breast cancer. Breast Cancer Res Treat. 2015;149:363-71 pubmed publisher
    ..particularly in basal-like breast cancer, and often occurs together with deletions of BRCA1, RB1, TP53, PTEN, and INPP4B. In this study, we investigate whether these co-deleted genes have interactive effects on survival in breast ..
  33. Zhang F, Zhu J, Li J, Zhu F, Zhang P. IRF2-INPP4B axis participates in the development of acute myeloid leukemia by regulating cell growth and survival. Gene. 2017;627:9-14 pubmed publisher
    ..Further mechanism analysis shows that inositol polyphosphate-4-phosphatase, type-II (INPP4B) contributes to the effects of IRF2 on apoptosis and growth of AML cells...
  34. Malek M, Kielkowska A, Chessa T, Anderson K, Barneda D, Pir P, et al. PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K. Mol Cell. 2017;68:566-580.e10 pubmed publisher
    ..PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which ..
  35. Choi E, Kim M, Yoo N, Lee S. Inactivating Frameshift Mutation of INPP4B Encoding a PI3K Pathway Phosphatase in Gastric and Colorectal Cancers. Pathol Oncol Res. 2016;22:653-4 pubmed publisher
  36. Dowling J, Becker C, Bourke N, Corr S, Connolly D, Quinn S, et al. Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation. J Biol Chem. 2014;289:6429-37 pubmed publisher
    ..Collectively, our data indicate that PML limits ASC function, retaining ASC in the nucleus. ..
  37. Asleh Aburaya K, Sheffield B, Kos Z, Won J, Wang X, Gao D, et al. Basal biomarkers nestin and INPP4b identify intrinsic subtypes accurately in breast cancers that are weakly positive for oestrogen receptor. Histopathology. 2017;70:185-194 pubmed publisher
    ..not dependent upon ER status - positive expression of nestin or loss of inositol polyphosphate-4-phosphatase (INPP4b) - to discriminate intrinsic subtypes, focusing on clinically problematic cases with weak ER positivity...
  38. Amato R, Pinelli M, Monticelli A, Miele G, Cocozza S. Schizophrenia and vitamin D related genes could have been subject to latitude-driven adaptation. BMC Evol Biol. 2010;10:351 pubmed publisher
    ..Finally, we discuss a model in which schizophrenia is, at least partly, a maladaptive by-product of latitude dependent adaptive changes in vitamin D metabolism. ..
  39. Chew C, Chen M, Pandolfi P. Endosome and INPP4B. Oncotarget. 2016;7:5-6 pubmed publisher
  40. Guo S, Chi M, Yang R, Guo X, Zan L, Wang C, et al. INPP4B is an oncogenic regulator in human colon cancer. Oncogene. 2016;35:3049-61 pubmed publisher
    Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers...
  41. Chen H, Li H, Chen Q. INPP4B overexpression suppresses migration, invasion and angiogenesis of human prostate cancer cells. Clin Exp Pharmacol Physiol. 2017;44:700-708 pubmed publisher
    Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumour suppressor in different human cancers. However, the role of INPP4B in the angiogenesis of human prostate cancer cells remains unclear...
  42. Ding H, Sun Y, Hou Y, Li L. Effects of INPP4B gene transfection combined with PARP inhibitor on castration therapy-resistant prostate cancer cell line, PC3. Urol Oncol. 2014;32:720-6 pubmed publisher
    This study investigated the effects of combining inositol polyphosphate-4-phosphatase type II (INPP4B) gene transfection with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor on castration therapy-resistant prostate cancer ..
  43. Ip L, Poulogiannis G, Viciano F, Sasaki J, Kofuji S, Spanswick V, et al. Loss of INPP4B causes a DNA repair defect through loss of BRCA1, ATM and ATR and can be targeted with PARP inhibitor treatment. Oncotarget. 2015;6:10548-62 pubmed
    ..The lipid phosphatase inositol polyphosphate 4-phosphatase type II (INPP4B) has been described as a tumor suppressor in the PI3K/Akt pathway with loss of expression found most pronounced in ..
  44. Rynkiewicz N, Fedele C, Chiam K, Gupta R, Kench J, Ooms L, et al. INPP4B is highly expressed in prostate intermediate cells and its loss of expression in prostate carcinoma predicts for recurrence and poor long term survival. Prostate. 2015;75:92-102 pubmed publisher
    ..Expression of INPP4B, another negative regulator of the PI3K/Akt pathway, is also reduced in prostate carcinoma...
  45. Reed D, Shokat K. INPP4B and PTEN Loss Leads to PI-3,4-P2 Accumulation and Inhibition of PI3K in TNBC. Mol Cancer Res. 2017;15:765-775 pubmed publisher
    ..Inositol polyphosphate-4-phosphatase type II (INPP4B) catalyzes the removal of the 4'-phosphate of phosphatidylinositol-(3, 4)-bisphosphate (PI-3,4-P2), creating ..
  46. Kofuji S, Kimura H, Nakanishi H, Nanjo H, Takasuga S, Liu H, et al. INPP4B Is a PtdIns(3,4,5)P3 Phosphatase That Can Act as a Tumor Suppressor. Cancer Discov. 2015;5:730-9 pubmed publisher
    Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumor suppressor mutated in human breast, ovary, and prostate cancers. The molecular mechanism underlying INPP4B's tumor-suppressive role is currently unknown...
  47. Min J, Kim K, Kim H, Kim E, Noh W, Jeon H, et al. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells. Biochem Biophys Res Commun. 2013;440:137-42 pubmed publisher
    Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype...
  48. Lemcke S, Müller S, Möller S, Schillert A, Ziegler A, Cepok Kauffeld S, et al. Nerve conduction velocity is regulated by the inositol polyphosphate-4-phosphatase II gene. Am J Pathol. 2014;184:2420-9 pubmed publisher
    ..silico haplotype analyses, and comparative genomics we identified inositol polyphosphate-4-phosphatase, type II (Inpp4b) as the quantitative trait gene for EAE31...
  49. Lopez S, Hodgson M, Packianathan C, Bingöl Özakpınar Ö, Uras F, Rosen B, et al. Determinants of the tumor suppressor INPP4B protein and lipid phosphatase activities. Biochem Biophys Res Commun. 2013;440:277-82 pubmed publisher
    The tumor suppressor INPP4B is an important regulator of phosphatidyl-inositol signaling in the cell. Reduced INPP4B expression is associated with poor outcomes for breast, prostate, and ovarian cancer patients...
  50. Zhang X, Majerus P. Phosphatidylinositol signalling reactions. Semin Cell Dev Biol. 1998;9:153-60 pubmed
    ..Surprisingly, they can synthesize PtdIns 3,4,5-P3 directly from PtdIns 3-P in a concerted reaction. PIP5K isozymes may play pivotal roles in intracellular signaling. ..
  51. Rampersaud E, Damcott C, Fu M, Shen H, McArdle P, Shi X, et al. Identification of novel candidate genes for type 2 diabetes from a genome-wide association scan in the Old Order Amish: evidence for replication from diabetes-related quantitative traits and from independent populations. Diabetes. 2007;56:3053-62 pubmed
    ..Our GWAS of type 2 diabetes identified several gene variants associated with type 2 diabetes, some of which are worthy of further study. ..
  52. Li Chew C, Lunardi A, Gulluni F, Ruan D, Chen M, Salmena L, et al. In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K-AKT Signaling at Endosomes. Cancer Discov. 2015;5:740-51 pubmed publisher
    The phosphatases PTEN and INPP4B have been proposed to act as tumor suppressors by antagonizing PI3K-AKT signaling and are frequently dysregulated in human cancer...
  53. Erneux C, Ghosh S, Ramos A, Edimo W. New Functions of the Inositol Polyphosphate 5-Phosphatases in Cancer. Curr Pharm Des. 2016;22:2309-14 pubmed
    ..5-phosphatases can be amplified in human cancer cells, whereas the 3- and 4- phosphatase tumor suppressor PTEN and INPP4B, repectively are often repressed or deleted...
  54. Chi M, Guo S, Wilmott J, Guo X, Yan X, Wang C, et al. INPP4B is upregulated and functions as an oncogenic driver through SGK3 in a subset of melanomas. Oncotarget. 2015;6:39891-907 pubmed publisher
    Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates PI3K/Akt signalling and has a tumour suppressive role in some types of cancers. However, we have found that it is upregulated in a subset of melanomas...
  55. Kim J, Yun H, Um H, Park J, Lee K, Kang C, et al. Identification of inositol polyphosphate 4-phosphatase type II as a novel tumor resistance biomarker in human laryngeal cancer HEp-2 cells. Cancer Biol Ther. 2012;13:1307-18 pubmed publisher
    ..In this study, we identified inositol polyphosphate 4-phosphatase type II (INPP4B) as a novel marker of radioresistance by systematically analyzing Unigene libraries of laryngeal cancer...
  56. Sueta A, Yamamoto Y, Yamamoto Ibusuki M, Hayashi M, Takeshita T, Yamamoto S, et al. An integrative analysis of PIK3CA mutation, PTEN, and INPP4B expression in terms of trastuzumab efficacy in HER2-positive breast cancer. PLoS ONE. 2014;9:e116054 pubmed publisher
    ..PIK3CA mutation and loss of phosphatase and tensin homolog (PTEN) and inositol polyphosphate 4-phosphatase-II (INPP4B)...
  57. Thomas C, Henry W, Cuiffo B, Collmann A, Marangoni E, Benhamo V, et al. Pentraxin-3 is a PI3K signaling target that promotes stem cell-like traits in basal-like breast cancers. Sci Signal. 2017;10: pubmed publisher
    ..catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II)...
  58. Tokunaga E, Yamashita N, Kitao H, Tanaka K, Taketani K, Inoue Y, et al. Biological and clinical significance of loss of heterozygosity at the INPP4B gene locus in Japanese breast cancer. Breast. 2016;25:62-8 pubmed publisher
    b>INPP4B is considered to function as a putative tumor suppressor through its inhibitory function of Akt...
  59. Hsu I, Yeh C, Slavin S, Miyamoto H, Netto G, Tsai Y, et al. Estrogen receptor alpha prevents bladder cancer via INPP4B inhibited akt pathway in vitro and in vivo. Oncotarget. 2014;5:7917-35 pubmed
    ..Mechanism studies suggest that ERα could control the expression of INPP4B to reduce AKT activity and consequently reduce BCa cell growth...
  60. Munday A, Norris F, Caldwell K, Brown S, Majerus P, Mitchell C. The inositol polyphosphate 4-phosphatase forms a complex with phosphatidylinositol 3-kinase in human platelet cytosol. Proc Natl Acad Sci U S A. 1999;96:3640-5 pubmed
    ..The majority of the PI 3-kinase/4-phosphatase complex (75%) remained in the cytosolic fraction. We propose that the complex formed between the two enzymes serves to localize the 4-phosphatase to sites of PtdIns(3,4)P2 production. ..
  61. Kanaya N, Somlo G, Wu J, Frankel P, Kai M, Liu X, et al. Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. J Steroid Biochem Mol Biol. 2017;170:65-74 pubmed publisher
    ..were divided into 2 groups by luminal A/B signature [protein expression of ER, AR, Bcl-2, Bim (BCL2L11), GATA3 and INPP4b], and this expression signature was also associated with the rate of PDX intake...
  62. Dzneladze I, Woolley J, Rossell C, Han Y, Rashid A, Jain M, et al. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML. PLoS ONE. 2018;13:e0191510 pubmed publisher
    Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival...
  63. Zhang L, Zeng D, Chen Y, Li N, Lv Y, Li Y, et al. miR-937 contributes to the lung cancer cell proliferation by targeting INPP4B. Life Sci. 2016;155:110-5 pubmed publisher
    ..Mechanism analyses found polyphosphate 4-phosphatase type II (INPP4B) was the target of miR-937, miR-937 directly bound to the 3'UTR of INPP4B, knockdown of INPP4B in A549 with miR-..
  64. Rijal S, Fleming S, Cummings N, Rynkiewicz N, Ooms L, Nguyen N, et al. Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML. Blood. 2015;125:2815-24 pubmed publisher
    ..3-phosphatase (PTEN), PtdIns(3,4,5)P3 5-phosphatases (eg, SHIP), and PtdIns(3,4)P2 4-phosphatases (eg, INPP4B)...
  65. Gasser J, Inuzuka H, Lau A, Wei W, Beroukhim R, Toker A. SGK3 mediates INPP4B-dependent PI3K signaling in breast cancer. Mol Cell. 2014;56:595-607 pubmed publisher
    ..in breast cancer and activated downstream of PIK3CA in a manner dependent on the phosphoinositide phosphatase INPP4B. Expression of INPP4B leads to enhanced SGK3 activation and suppression of Akt phosphorylation...
  66. Strotbek M, Schmid S, Sánchez González I, Boerries M, Busch H, Olayioye M. miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer. Int J Cancer. 2017;140:2310-2320 pubmed publisher
    ..We show that miR-181a and miR-181d posttranscriptionally suppress the expression of PHLPP2 and INPP4B phosphatases, resulting in elevated growth factor-induced Akt phosphorylation...
  67. Wang P, Ma D, Wang J, Fang Q, Gao R, Wu W, et al. INPP4B-mediated DNA repair pathway confers resistance to chemotherapy in acute myeloid leukemia. Tumour Biol. 2016;37:12513-12523 pubmed
    b>INPP4B has been recently shown to be a poor prognostic marker and confer chemo- or radio-resistance in AML cells, whereas, the underlying mechanisms remain unclear...
  68. Dzneladze I, He R, Woolley J, Son M, Sharobim M, Greenberg S, et al. INPP4B overexpression is associated with poor clinical outcome and therapy resistance in acute myeloid leukemia. Leukemia. 2015;29:1485-95 pubmed publisher
    In this study, we investigated the role of inositol polyphosphate-4-phosphatase, type-II (INPP4B) in acute myeloid leukemia (AML)...
  69. Chen H, Li H, Chen Q. INPP4B reverses docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer. Biochem Biophys Res Commun. 2016;477:467-72 pubmed publisher
    ..Recent studies have implied a role of INPP4B in tumor chemoresistance, while the effects of INPP4B on docetaxel resistance in PCa have not been elucidated...
  70. Croft A, Guo S, Sherwin S, Farrelly M, Yan X, Zhang X, et al. Functional identification of a novel transcript variant of INPP4B in human colon and breast cancer cells. Biochem Biophys Res Commun. 2017;485:47-53 pubmed publisher
    The 4-phosphatase Inositol polyphosphate 4-phosphatase II (INPP4B) is a regulator of the PI3K signalling pathway and functions to suppress or promote activation of downstream kinases depending on cell type and context...