oncogenes

Summary

Summary: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.

Top Publications

  1. Schulze A, Harris A. How cancer metabolism is tuned for proliferation and vulnerable to disruption. Nature. 2012;491:364-73 pubmed publisher
    ..The identification of metabolic weaknesses of cancer cells has been used to create strategies for treating cancer, but there are still challenges to be faced in bringing the drugs that target cancer metabolism to the clinic. ..
  2. Friedmann Morvinski D, Bushong E, Ke E, Soda Y, Marumoto T, Singer O, et al. Dedifferentiation of neurons and astrocytes by oncogenes can induce gliomas in mice. Science. 2012;338:1080-4 pubmed publisher
  3. Stella G, Luisetti M, Pozzi E, Comoglio P. Oncogenes in non-small-cell lung cancer: emerging connections and novel therapeutic dynamics. Lancet Respir Med. 2013;1:251-61 pubmed publisher
    ..This Review aims to highlight the functional associations between key oncogenes that drive lung tumorigenesis and are distinct targetable molecules...
  4. Martinez Outschoorn U, Curry J, Ko Y, Lin Z, Tuluc M, Cognetti D, et al. Oncogenes and inflammation rewire host energy metabolism in the tumor microenvironment: RAS and NF?B target stromal MCT4. Cell Cycle. 2013;12:2580-97 pubmed publisher
    ..epithelial cell lines were co-cultured with human fibroblasts, to determine the "bystander" effects of oncogenes on stromal cells. ROS production and glucose uptake were measured by FACS analysis...
  5. Pattabiraman D, McGirr C, Shakhbazov K, Barbier V, Krishnan K, Mukhopadhyay P, et al. Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes. Blood. 2014;123:2682-90 pubmed publisher
    ..allele of c-Myb, we show that this interaction is essential for in vitro transformation by the myeloid leukemia oncogenes AML1-ETO, AML1-ETO9a, MLL-ENL, and MLL-AF9...
  6. Cladel N, Budgeon L, Hu J, Balogh K, Christensen N. Synonymous codon changes in the oncogenes of the cottontail rabbit papillomavirus lead to increased oncogenicity and immunogenicity of the virus. Virology. 2013;438:70-83 pubmed publisher
    ..We changed rare codons in the oncogenes E6 and E7 of the cottontail rabbit papillomavirus to make them more mammalian-like and tested the mutant genomes ..
  7. Neelsen K, Zanini I, Herrador R, Lopes M. Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates. J Cell Biol. 2013;200:699-708 pubmed publisher
    ..We propose that nucleolytic processing of unusual replication intermediates mediates oncogene-induced genotoxicity and that limiting such processing to mitosis is a central anti-tumorigenic function of the DNA damage checkpoints. ..
  8. Gylfe A, Kondelin J, Turunen M, Ristolainen H, Katainen R, Pitkänen E, et al. Identification of candidate oncogenes in human colorectal cancers with microsatellite instability. Gastroenterology. 2013;145:540-3.e22 pubmed publisher
    Microsatellite instability can be found in approximately 15% of all colorectal cancers. To detect new oncogenes we sequenced the exomes of 25 colorectal tumors and respective healthy colon tissue...
  9. Oikonomou E, Pintzas A. The TRAIL of oncogenes to apoptosis. Biofactors. 2013;39:343-54 pubmed publisher
    ..Remarkably, RAS, MYC and HER2 oncogenes have been shown to sensitise tumor cells to TRAIL induced cell death...

More Information

Publications62

  1. Cros J, Sbidian E, Hans S, Roussel H, Scotte F, Tartour E, et al. Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours. Ann Oncol. 2013;24:2624-9 pubmed publisher
    ..Patients with advanced disease may benefit from targeted therapy; however, specific targets for optimising and personalising treatments are yet to be identified...
  2. Gamage D, Hendrickson T. GPI transamidase and GPI anchored proteins: oncogenes and biomarkers for cancer. Crit Rev Biochem Mol Biol. 2013;48:446-64 pubmed publisher
    ..Given that functions for only one of GPI-T's subunits have been robustly assigned, the separation between healthy and malignant GPI-T activity is poorly defined. ..
  3. Bottos A, Bardelli A. Oncogenes and angiogenesis: a way to personalize anti-angiogenic therapy?. Cell Mol Life Sci. 2013;70:4131-40 pubmed publisher
    ..However, as we highlight in this review, activated oncogenes and deregulated angiogenesis are tightly associated, as mutations in cancer cells can lead to perturbation of ..
  4. Huang G, Singh B. Coamplification and cooperation: toward identifying biologically relevant oncogenes. Clin Cancer Res. 2013;19:5549-51 pubmed publisher
    ..Assessing for coactivation of functionally related genes resulted in the identification of SENP2, DCUN1D1, and DVL3--consensus candidates that drive selection for 3q amplification in lung squamous cell carcinomas. ..
  5. Yuan L, Tian T, Chen Y, Yan S, Xing X, Zhang Z, et al. Existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy. Sci Rep. 2013;3:1811 pubmed publisher
    ..We reported our findings for the existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy...
  6. Vicente Dueñas C, Romero Camarero I, Cobaleda C, Sanchez Garcia I. Function of oncogenes in cancer development: a changing paradigm. EMBO J. 2013;32:1502-13 pubmed publisher
    Tumour-associated oncogenes induce unscheduled proliferation as well as genomic and chromosomal instability. According to current models, therapeutic strategies that block oncogene activity are likely to selectively target tumour cells...
  7. Lu R, Ji Z, Li X, Zhai Q, Zhao C, Jiang Z, et al. miR-145 functions as tumor suppressor and targets two oncogenes, ANGPT2 and NEDD9, in renal cell carcinoma. J Cancer Res Clin Oncol. 2014;140:387-97 pubmed publisher
    ..We further validated those miR-145 targets two oncogenes, ANGPT2 and NEDD9 in RCC. In addition, miR-145 was found to regulate numerous genes involved in the EMT...
  8. Oxnard G, Binder A, Janne P. New targetable oncogenes in non-small-cell lung cancer. J Clin Oncol. 2013;31:1097-104 pubmed publisher
    ..lymphoma kinase tyrosine kinase inhibitors has led to a surge of interest in identifying additional targetable oncogenes in non-small-cell lung cancer...
  9. Lisanti M, Martinez Outschoorn U, Sotgia F. Oncogenes induce the cancer-associated fibroblast phenotype: metabolic symbiosis and "fibroblast addiction" are new therapeutic targets for drug discovery. Cell Cycle. 2013;12:2723-32 pubmed publisher
    ..b>Oncogenes drive the onset of the cancer-associated fibroblast phenotype in adjacent normal fibroblasts via paracrine ..
  10. Lawrence M, Stojanov P, Polak P, Kryukov G, Cibulskis K, Sivachenko A, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214-218 pubmed publisher
    ..By incorporating mutational heterogeneity into the analyses, MutSigCV is able to eliminate most of the apparent artefactual findings and enable the identification of genes truly associated with cancer. ..
  11. Griaud F, Pierce A, Gonzalez Sanchez M, Scott M, Abraham S, Holyoake T, et al. A pathway from leukemogenic oncogenes and stem cell chemokines to RNA processing via THOC5. Leukemia. 2013;27:932-40 pubmed publisher
    ..pathways for THOC5 phosphorylation to develop an understanding of THO complex modulation by tyrosine kinase (TK) oncogenes in leukemias...
  12. Kandoth C, McLellan M, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502:333-339 pubmed publisher
    ..Taken together, these results lay the groundwork for developing new diagnostics and individualizing cancer treatment. ..
  13. Zhang Y, Xia J, Zhang Y, Qin Y, Yang D, Qi L, et al. Pitfalls in experimental designs for characterizing the transcriptional, methylational and copy number changes of oncogenes and tumor suppressor genes. PLoS ONE. 2013;8:e58163 pubmed publisher
    ..to characterize the transcriptional, methylational and/or copy number changes of pre-defined candidate oncogenes or tumor suppressor genes (TSGs), although some examples are known that carcinogenic mutants may express and ..
  14. Hirata H, Ueno K, Shahryari V, Tanaka Y, Tabatabai Z, Hinoda Y, et al. Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer. PLoS ONE. 2012;7:e51056 pubmed publisher
    ..In conclusion, our data suggests that miR-182-5p plays an important role as an oncogene by knocking down RECK and Smad4, resulting in activation of the Wnt-beta-catenin signaling pathway in bladder cancer. ..
  15. Rathje L, Nordgren N, Pettersson T, Rönnlund D, Widengren J, Aspenstrom P, et al. Oncogenes induce a vimentin filament collapse mediated by HDAC6 that is linked to cell stiffness. Proc Natl Acad Sci U S A. 2014;111:1515-20 pubmed publisher
    b>Oncogenes deregulate fundamental cellular functions, which can lead to development of tumors, tumor-cell invasion, and metastasis...
  16. Sumazin P, Yang X, Chiu H, Chung W, Iyer A, Llobet Navas D, et al. An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell. 2011;147:370-81 pubmed publisher
    ..Thus, miR-mediated interactions provide a mechanistic, experimentally validated rationale for the loss of PTEN expression in a large number of glioma samples with an intact PTEN locus. ..
  17. Dang C. Links between metabolism and cancer. Genes Dev. 2012;26:877-90 pubmed publisher
    Metabolism generates oxygen radicals, which contribute to oncogenic mutations. Activated oncogenes and loss of tumor suppressors in turn alter metabolism and induce aerobic glycolysis...
  18. Engelmann J, Spang R. A least angle regression model for the prediction of canonical and non-canonical miRNA-mRNA interactions. PLoS ONE. 2012;7:e40634 pubmed publisher
    ..In addition, we found genes involved in DNA recombination and repair that underline its importance in maintaining the integrity of the cell. ..
  19. Homminga I, Pieters R, Langerak A, de Rooi J, Stubbs A, Verstegen M, et al. Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia. Cancer Cell. 2011;19:484-97 pubmed publisher
    ..Two T-ALL subtypes were identified that lacked rearrangements of known oncogenes. One subtype associated with cortical arrest, expression of cell cycle genes, and ectopic NKX2-1 or NKX2-2 ..
  20. Stephens P, Tarpey P, Davies H, Van Loo P, Greenman C, Wedge D, et al. The landscape of cancer genes and mutational processes in breast cancer. Nature. 2012;486:400-4 pubmed publisher
    ..Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease. ..
  21. Laudanski P, Kowalczuk O, Klasa Mazurkiewicz D, Milczek T, Rysak Luberowicz D, Garbowicz M, et al. Selective gene expression profiling of mTOR-associated tumor suppressor and oncogenes in ovarian cancer. Folia Histochem Cytobiol. 2011;49:317-24 pubmed
    ..this study was to selectively profile the activation status of mammalian target of rapamycin (mTOR)-associated oncogenes and tumor suppressor genes (TSGs) in ovarian cancer specimens, healthy ovaries and benign ovarian tumors, ..
  22. Yuan Y, Curtis C, Caldas C, Markowetz F. A sparse regulatory network of copy-number driven gene expression reveals putative breast cancer oncogenes. IEEE/ACM Trans Comput Biol Bioinform. 2012;9:947-54 pubmed publisher
    Copy number aberrations are recognized to be important in cancer as they may localize to regions harboring oncogenes or tumor suppressors. Such genomic alterations mediate phenotypic changes through their impact on expression...
  23. Schoppy D, Ragland R, Gilad O, Shastri N, Peters A, Murga M, et al. Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR. J Clin Invest. 2012;122:241-52 pubmed publisher
  24. Suh Y, Post S, Elizondo Fraire A, Maccio D, Jackson J, El Naggar A, et al. Multiple stress signals activate mutant p53 in vivo. Cancer Res. 2011;71:7168-75 pubmed publisher
    ..In this report, we examined the role of oncogenes, DNA damage, and reactive oxygen species, signals that stabilize wild-type p53, on the stabilization of mutant ..
  25. Jiang Y, Chen L. microRNAs as tumor inhibitors, oncogenes, biomarkers for drug efficacy and outcome predictors in lung cancer (review). Mol Med Rep. 2012;5:890-4 pubmed publisher
    ..In the present study, we discuss the potential of miRNAs to function as suppressors and biomarkers for chemoresistance and prognosis of lung cancer. ..
  26. Berger M, Hodis E, Heffernan T, Deribe Y, Lawrence M, Protopopov A, et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature. 2012;485:502-6 pubmed publisher
    ..Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma. ..
  27. Choy E, Hornicek F, MacConaill L, Harmon D, Tariq Z, Garraway L, et al. High-throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide-3-kinase and other oncogenes. Cancer. 2012;118:2905-14 pubmed publisher
    ..The authors identified somatic nonsynonymous coding mutations in oncogenes associated with human cancers and hotspot mutations from tumor suppressor genes that were either well described ..
  28. Jones R, Mortusewicz O, Afzal I, Lorvellec M, Garcia P, Helleday T, et al. Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. Oncogene. 2013;32:3744-53 pubmed publisher
    It has become increasingly clear that oncogenes not only provide aberrant growth signals to cells but also cause DNA damage at replication forks (replication stress), which activate the ataxia telangiectasia mutated (ATM)/p53-dependent ..
  29. Shao C, Sun W, Tan M, Glazer C, Bhan S, Zhong X, et al. Integrated, genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma. Clin Cancer Res. 2011;17:4320-30 pubmed publisher
    ..Our integrated, genome-wide screening method proved to be an effective strategy for detecting novel oncogenes in ACC...
  30. Harburg G, Hinck L. Navigating breast cancer: axon guidance molecules as breast cancer tumor suppressors and oncogenes. J Mammary Gland Biol Neoplasia. 2011;16:257-70 pubmed publisher
    ..during tumorigenesis and tumor progression suggests that AGMs also play a crucial role as tumor suppressors and oncogenes in breast cancer...
  31. Chen S, Xu Y, Chen Y, Li X, Mou W, Wang L, et al. SOX2 gene regulates the transcriptional network of oncogenes and affects tumorigenesis of human lung cancer cells. PLoS ONE. 2012;7:e36326 pubmed publisher
    ..In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2, and NOTCH1 was detected in side population (SP) cells than in non-side population (NSP) cells ..
  32. Trinh X, Tjalma W, Dirix L, Vermeulen P, Peeters D, Bachvarov D, et al. Microarray-based oncogenic pathway profiling in advanced serous papillary ovarian carcinoma. PLoS ONE. 2011;6:e22469 pubmed publisher
    ..These findings may indicate opposite confounding of prognostic versus predictive factors when studying biomarkers in epithelial ovarian cancer. ..
  33. Murfuni I, Nicolai S, Baldari S, Crescenzi M, Bignami M, Franchitto A, et al. The WRN and MUS81 proteins limit cell death and genome instability following oncogene activation. Oncogene. 2013;32:610-20 pubmed publisher
  34. Scott K, Nogueira C, Heffernan T, van Doorn R, Dhakal S, Hanna J, et al. Proinvasion metastasis drivers in early-stage melanoma are oncogenes. Cancer Cell. 2011;20:92-103 pubmed publisher
    ..Furthermore, we show that one such gene, ACP5, confers spontaneous metastasis in vivo, engages a key pathway governing metastasis, and is prognostic in human primary melanomas. ..
  35. Ying J, Shan L, Li J, Zhong L, Xue L, Zhao H, et al. Genome-wide screening for genetic alterations in esophageal cancer by aCGH identifies 11q13 amplification oncogenes associated with nodal metastasis. PLoS ONE. 2012;7:e39797 pubmed publisher
    ..and homozygous deletions, directly contribute to tumorigenesis through altering the expression of key oncogenes and tumor suppressor genes...
  36. Wrzeszczynski K, Varadan V, Byrnes J, Lum E, Kamalakaran S, Levine D, et al. Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer. PLoS ONE. 2011;6:e28503 pubmed publisher
    ..interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor...
  37. Dooley A, Winslow M, Chiang D, Banerji S, Stransky N, Dayton T, et al. Nuclear factor I/B is an oncogene in small cell lung cancer. Genes Dev. 2011;25:1470-5 pubmed publisher
    ..Functional studies indicate that NFIB regulates cell viability and proliferation during transformation. ..
  38. Both J, Wu T, Bras J, Schaap G, Baas F, Hulsebos T. Identification of novel candidate oncogenes in chromosome region 17p11.2-p12 in human osteosarcoma. PLoS ONE. 2012;7:e30907 pubmed publisher
    ..2-p12 is amplified in about 25% of cases. In previous studies, COPS3 and PMP22 have been identified as candidate oncogenes in this region...
  39. Musgrove E, Caldon C, Barraclough J, Stone A, Sutherland R. Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 2011;11:558-72 pubmed publisher
    ..Is this an effective means of targeting the cyclin D oncogenes, and how might the patient subgroups that are most likely to benefit be identified?
  40. Zhao M, Sun J, Zhao Z. Distinct and competitive regulatory patterns of tumor suppressor genes and oncogenes in ovarian cancer. PLoS ONE. 2012;7:e44175 pubmed publisher
    So far, investigators have found numerous tumor suppressor genes (TSGs) and oncogenes (OCGs) that control cell proliferation and apoptosis during cancer development...
  41. Chiyomaru T, Yamamura S, Zaman M, Majid S, Deng G, Shahryari V, et al. Genistein suppresses prostate cancer growth through inhibition of oncogenic microRNA-151. PLoS ONE. 2012;7:e43812 pubmed publisher
    ..This study suggests that genistein mediated suppression of oncogenic miRNAs can be an important dietary therapeutic strategy for the treatment of PCa. ..
  42. Wei X, Walia V, Lin J, Teer J, Prickett T, Gartner J, et al. Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet. 2011;43:442-6 pubmed publisher
    ..Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease. ..
  43. Magudia K, Lahoz A, Hall A. K-Ras and B-Raf oncogenes inhibit colon epithelial polarity establishment through up-regulation of c-myc. J Cell Biol. 2012;198:185-94 pubmed publisher
    KRAS, BRAF, and PI3KCA are the most frequently mutated oncogenes in human colon cancer. To explore their effects on morphogenesis, we used the colon cancer-derived cell line Caco-2...
  44. Fernandez A, Huidobro C, Fraga M. De novo DNA methyltransferases: oncogenes, tumor suppressors, or both?. Trends Genet. 2012;28:474-9 pubmed publisher
    ..activity at advanced tumor stages leads to the promoter DNA demethylation-dependent expression of specific oncogenes. These new data support the notion that de novo DNMTs also have an important role in the maintenance of DNA ..
  45. DeNicola G, Karreth F, Humpton T, Gopinathan A, Wei C, Frese K, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 2011;475:106-9 pubmed publisher
    ..of endogenous oncogenic alleles of Kras, Braf and Myc, and found that ROS are actively suppressed by these oncogenes. K-Ras(G12D), B-Raf(V619E) and Myc(ERT2) each increased the transcription of Nrf2 to stably elevate the basal ..
  46. Suárez A, Kong R, George T, He L, Yue Z, van Dyk L. Gammaherpesvirus 68 infection of endothelial cells requires both host autophagy genes and viral oncogenes for optimal survival and persistence. J Virol. 2011;85:6293-308 pubmed publisher
    ..Furthermore, we identified two viral oncogenes, v-cyclin and v-Bcl2, that are critical to EC survival and that modify EC proliferation and survival during ..
  47. Kim K, Chadalapaka G, Lee S, Yamada D, Sastre Garau X, Defossez P, et al. Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene. 2012;31:1034-44 pubmed publisher
    ..of the specificity protein 1 (Sp1), Sp3 and Sp4 genes, and subsequent downregulation of several Sp-dependent oncogenes, in part, through competition between ZBTB4 and Sp transcription factors for GC-rich promoter sequences...
  48. Lujambio A, Lowe S. The microcosmos of cancer. Nature. 2012;482:347-55 pubmed publisher
    ..in cancer, in which they can function as a group to mark differentiation states or individually as bona fide oncogenes or tumour suppressors...
  49. Chatterjee S, Seifried L, Feigin M, Gibbons D, Scuoppo C, Lin W, et al. Dysregulation of cell polarity proteins synergize with oncogenes or the microenvironment to induce invasive behavior in epithelial cells. PLoS ONE. 2012;7:e34343 pubmed publisher
    ..Here, we report that loss of polarity protein expression in epithelial cells primes them for cooperation with oncogenes or changes in tissue microenvironment to promote invasive behavior...
  50. Concepcion C, Bonetti C, Ventura A. The microRNA-17-92 family of microRNA clusters in development and disease. Cancer J. 2012;18:262-7 pubmed publisher
    ..Finally, we discuss the current evidence suggesting how the different miRNAs encoded by these 3 clusters can functionally cooperate to fine-tune signaling and developmental pathways. ..
  51. Nohata N, Hanazawa T, Kinoshita T, Okamoto Y, Seki N. MicroRNAs function as tumor suppressors or oncogenes: aberrant expression of microRNAs in head and neck squamous cell carcinoma. Auris Nasus Larynx. 2013;40:143-9 pubmed publisher
    ..We discuss recent findings on the aberrant expression of miRNAs and their contribution to human HNSCC oncogenesis. ..
  52. Chen J, Russo J. Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells. Biochim Biophys Acta. 2012;1826:370-84 pubmed publisher
    ..involved in the key regulatory steps of glucose transport, glycolysis, TCA cycle and glutaminolysis by several oncogenes including c-Myc and hypoxia inducible factor-1 (HIF-1) and tumor suppressor, p53, in cancer cells...
  53. Xie T, D ario G, Lamb J, Martin E, Wang K, Tejpar S, et al. A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations. PLoS ONE. 2012;7:e42001 pubmed publisher
    ..1 was identified (p<0.01). Focal aberrations identified by the GISTIC method confirmed amplifications of oncogenes including EGFR, ERBB2, CCND1, MET, and MYC, and deletions of tumor suppressors including TP53, APC, and SMAD4, ..