Genomes and Genes
Summary: A family of intercellular signaling proteins that play an important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.
- El Shahawy M, Reibring C, Neben C, Hallberg K, Marangoni P, Harfe B, et al. Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid. PLoS Genet. 2017;13:e1006914 pubmed publisher..These findings reveal key functions for SHH and RA in cell fate specification in the lingual epithelium and aid in deciphering the molecular mechanisms that assign cell identity. ..
- Hu G, Wang T, Liu J, Chen Z, Zhong L, Yu S, et al. Serum protein expression profiling and bioinformatics analysis in workers occupationally exposed to chromium (VI). Toxicol Lett. 2017;277:76-83 pubmed publisher..Also, the current study preliminarily paved the way to further functional studies to understand the underlying mechanisms and novel serum biomarkers of Cr(VI) exposure. ..
- Ghouleh I, Sahoo S, Meijles D, Amaral J, de Jesus D, Sembrat J, et al. Endothelial Nox1 oxidase assembly in human pulmonary arterial hypertension; driver of Gremlin1-mediated proliferation. Clin Sci (Lond). 2017;131:2019-2035 pubmed publisher..These findings also support targeting of Nox1 as a viable therapeutic option to combat PAH. ..
- Yang N, Zhou T, Lei X, Wang C, Yan M, Wang Z, et al. Inhibition of Sonic Hedgehog Signaling Pathway by Thiazole Antibiotic Thiostrepton Attenuates the CD44+/CD24-Stem-Like Population and Sphere-Forming Capacity in Triple-Negative Breast Cancer. Cell Physiol Biochem. 2016;38:1157-70 pubmed publisher..Our results give a new insight into the mechanism of thiostrepton anti-tumor activity and suggest thiostrepton as a promising agent that targets hedgehog signaling pathway in TNBC. ..
- Ptaschinski C, Hrycaj S, Schaller M, Wellik D, Lukacs N. Hox5 Paralogous Genes Modulate Th2 Cell Function during Chronic Allergic Inflammation via Regulation of Gata3. J Immunol. 2017;199:501-509 pubmed publisher..These results reveal a novel role for Hox5 genes as developmental regulators of Th2 immune cell function that demonstrates a redeployment of mesenchyme-associated developmental genes. ..
- Zhou J, Chen Q, Lanske B, Fleming B, Terek R, Wei X, et al. Disrupting the Indian hedgehog signaling pathway in vivo attenuates surgically induced osteoarthritis progression in Col2a1-CreERT2; Ihhfl/fl mice. Arthritis Res Ther. 2014;16:R11 pubmed publisher..Thus, our findings suggest the potential to develop new therapeutic strategies that can prevent and treat OA by inhibiting Ihh signaling in chondrocytes. ..
- Huang J, Reilein A, Kalderon D. Yorkie and Hedgehog independently restrict BMP production in escort cells to permit germline differentiation in the Drosophila ovary. Development. 2017;144:2584-2594 pubmed publisher..Thus, both the coupling and output of the Hh and Yki signaling pathways differ between FSCs and ECs despite their proximity and the fact that FSCs give rise directly to ECs. ..
- Lin Y, Huang Y, He J, Chen F, He Y, Zhang W. Role of Hedgehog-Gli1 signaling in the enhanced proliferation and differentiation of MG63 cells enabled by hierarchical micro-/nanotextured topography. Int J Nanomedicine. 2017;12:3267-3280 pubmed publisher..These findings may aid in the optimization of hierarchical biomaterial topographies targeting Hedgehog-Gli1 signaling. ..
- Montagna E, Lopes O. Molecular basis of basal cell carcinoma. An Bras Dermatol. 2017;92:517-520 pubmed publisher..The cellular Hedgehog signaling pathway is activated in organogenesis, but is altered in various types of tumors. ..
- Riaz S, Ye L, Sahar N, Aman D, Qadir J, Khan J, et al. Transcriptional Profiling of Sonic Hedgehog in a Prospective Cohort of Breast Cancer in a Pakistani Population. Anticancer Res. 2017;37:4449-4454 pubmed..Furthermore, both luminal-B and triple-negative subtypes of cohort showed increased expression of SHH. Based on these findings, SHH may be used as a potential biomarker for breast carcinogenesis. ..
- Jiang J. CK1 in Developmental Signaling: Hedgehog and Wnt. Curr Top Dev Biol. 2017;123:303-329 pubmed publisher..I will highlight this feature in the context of Hh signaling and draw interesting parallels between the Hh and Wnt pathways. ..
- Wang F, Li Y, Wu X, Yang M, Cong W, Fan Z, et al. Transcriptome analysis of coding and long non-coding RNAs highlights the regulatory network of cascade initiation of permanent molars in miniature pigs. BMC Genomics. 2017;18:148 pubmed publisher..Our data provide fundamental knowledge and a basis for understanding the molecular mechanisms governing cascade initiation of additional molars, but also provide an important resource for developmental biology research. ..
- Salem O, Wang H, Alaseem A, Ciobanu O, Hadjab I, Gawri R, et al. Naproxen affects osteogenesis of human mesenchymal stem cells via regulation of Indian hedgehog signaling molecules. Arthritis Res Ther. 2014;16:R152 pubmed publisher..Therefore, Npx could affect MSC-mediated repair of subchondral bone in OA patients. ..
- Hebrok M, Kim S, Melton D. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev. 1998;12:1705-13 pubmed..Prevention of SHH expression in prepancreatic dorsal endoderm by intercellular signals, like activin and FGF, may be critical for permitting early steps of chick pancreatic development. ..
- Chen W, Huang H, Hatori R, Kornberg T. Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc. Development. 2017;144:3134-3144 pubmed publisher..These findings show that in the wing disc, Hh distributions and signaling are dependent upon basal release and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion was obtained. ..
- Ueda T, Tsubamoto H, Inoue K, Sakata K, Shibahara H, Sonoda T. Itraconazole Modulates Hedgehog, WNT/?-catenin, as well as Akt Signalling, and Inhibits Proliferation of Cervical Cancer Cells. Anticancer Res. 2017;37:3521-3526 pubmed..Immunoblots showed suppression in ?-catenin expression and Akt phosphorylation. Itraconazole is a multi-targeting anticancer agent and a promising therapeutic agent for cervical cancer. ..
- Wang C, Li J, Meng Q, Wang B. Three Tctn proteins are functionally conserved in the regulation of neural tube patterning and Gli3 processing but not ciliogenesis and Hedgehog signaling in the mouse. Dev Biol. 2017;430:156-165 pubmed publisher..These results suggest that Tctn1, Tctn2, and Tctn3 are functionally divergent with respect to their role in ciliogenesis and Hh signaling but conserved in neural tube patterning and Gli3 processing. ..
- De Mori R, Romani M, D Arrigo S, Zaki M, Lorefice E, Tardivo S, et al. Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects. Am J Hum Genet. 2017;101:552-563 pubmed publisher..We demonstrate that germline hypomorphic variants of SUFU cause deregulation of SHH signaling, resulting in recessive developmental defects of the CNS and limbs which share features with both SHH-related disorders and ciliopathies. ..
- Guerrero Flores G, Bastidas Ponce A, Collazo Navarrete O, Guerra Crespo M, Covarrubias L. Functional determination of the differentiation potential of ventral mesencephalic neural precursor cells during dopaminergic neurogenesis. Dev Biol. 2017;429:56-70 pubmed publisher..Based on our findings we propose that during DA differentiation committed vmNPCs emerge at E10.5 and they exhaust their neurogenic capacity with the rise of NPCs with astrogenic potential. ..
- Kopinke D, Roberson E, Reiter J. Ciliary Hedgehog Signaling Restricts Injury-Induced Adipogenesis. Cell. 2017;170:340-351.e12 pubmed publisher..We conclude that ciliary Hh signaling by FAPs orchestrates the regenerative response to skeletal muscle injury. ..
- Han Y, Xiong Y, Shi X, Wu J, Zhao Y, Jiang J. Regulation of Gli ciliary localization and Hedgehog signaling by the PY-NLS/karyopherin-?2 nuclear import system. PLoS Biol. 2017;15:e2002063 pubmed publisher..Our study unravels the molecular mechanism and cellular machinery regulating Gli ciliary localization and identifies Kap?2 as a critical regulator of the Hh pathway and a potential drug target for Hh-driven cancers. ..
- Deshmukh A, Binju M, Arfuso F, Newsholme P, Dharmarajan A. Role of epigenetic modulation in cancer stem cell fate. Int J Biochem Cell Biol. 2017;90:9-16 pubmed publisher..We have presented various aspects and examples of how epigenetic modulation may drive or promote tumorigenesis and metastasis by alteration of key transcriptomic programs and signaling pathways in CSCs. ..
- Ding J, Zhou X, Zou H, Wu J. Hedgehog signaling pathway affects the sensitivity of hepatoma cells to drug therapy through the ABCC1 transporter. Lab Invest. 2017;97:819-832 pubmed publisher..Hedgehog signaling transcription factor Gli-2 appears to be the primary regulator for drug sensitivity of hepatoma through the ABCC1 transporter. ..
- van Vliet P, Lin L, Boogerd C, Martin J, Andelfinger G, Grossfeld P, et al. Tissue specific requirements for WNT11 in developing outflow tract and dorsal mesenchymal protrusion. Dev Biol. 2017;429:249-259 pubmed publisher..These studies revealed a previously unappreciated role for WNT11 for DMP formation and distinct tissue-specific requirements for WNT11 in outflow tract and DMP development. ..
- Zou Q, Yang Z, Li D, Liu Z, Yuan Y. Association of chloride intracellular channel 4 and Indian hedgehog proteins with survival of patients with pancreatic ductal adenocarcinoma. Int J Exp Pathol. 2016;97:422-429 pubmed publisher..Thus CLIC4 and Ihh could serve as biological markers for the progression, metastasis and/or invasiveness of pancreatic ductal adenocarcinoma. ..
- Schock E, Brugmann S. Neural crest cells utilize primary cilia to regulate ventral forebrain morphogenesis via Hedgehog-dependent regulation of oriented cell division. Dev Biol. 2017;431:168-178 pubmed publisher..Together, these data suggest a novel, cilia-dependent mechanism for NCCs during forebrain development. ..
- Gaiano N, Kohtz J, Turnbull D, Fishell G. A method for rapid gain-of-function studies in the mouse embryonic nervous system. Nat Neurosci. 1999;2:812-9 pubmed..5 with a virus expressing Sonic Hedgehog. Infected embryos showed gross morphological brain defects, as well as ectopic expression of ventral telencephalic markers characteristic of either the medial or lateral ganglionic eminences. ..
- Hoelzl M, Heby Henricson K, Gerling M, Dias J, Kuiper R, Trünkle C, et al. Differential requirement of SUFU in tissue development discovered in a hypomorphic mouse model. Dev Biol. 2017;429:132-146 pubmed publisher..Our data demonstrate that tissue development is differentially affected in response to the reduced SUFU levels, providing novel insight regarding the requirements of different levels of SUFU for proper organogenesis. ..
- Pinskey J, Franks N, McMellen A, Giger R, Allen B. Neuropilin-1 promotes Hedgehog signaling through a novel cytoplasmic motif. J Biol Chem. 2017;292:15192-15204 pubmed publisher..These insights have implications for the development of novel modulators of HH-driven developmental disorders and diseases. ..
- de Jong D, Lopez C, Marrink S. Molecular view on protein sorting into liquid-ordered membrane domains mediated by gangliosides and lipid anchors. Faraday Discuss. 2013;161:347-63; discussion 419-59 pubmed..In addition, we probed the role of the ganglioside lipid GM1 on the protein sorting, showing formation of GM1-protein nano-domains that act as shuttles between the differently ordered membrane regions. ..
- Toriyama M, Toriyama M, Wallingford J, Finnell R. Folate-dependent methylation of septins governs ciliogenesis during neural tube closure. FASEB J. 2017;31:3622-3635 pubmed publisher..Toriyama, M., Toriyama, M., Wallingford, J. B., Finnell, R. H. Folate-dependent methylation of septins governs ciliogenesis during neural tube closure. ..
- Ingham P, McMahon A. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15:3059-87 pubmed
- Okuhashi Y, Itoh M, Tohda S. Hedgehog Stimulation Suppresses Clonogenicity and Activates NOTCH Signalling in T-lymphoblastic Leukaemia Jurkat Cells. Anticancer Res. 2017;37:5005-5009 pubmed..However, no such effects were observed in KOPT-K1 cells. Our results indicate that SHH stimulation activates NOTCH signalling in Jurkat cells, thus disclosing a novel relationship between HH and NOTCH pathways. ..
- Will A, Cova G, Osterwalder M, Chan W, Wittler L, Brieske N, et al. Composition and dosage of a multipartite enhancer cluster control developmental expression of Ihh (Indian hedgehog). Nat Genet. 2017;49:1539-1545 pubmed publisher..Thus, precise spatiotemporal control of developmental gene expression is achieved by complex multipartite enhancer ensembles. Alterations in the composition of such clusters can result in gene misexpression and disease. ..
- Steinert A, Weissenberger M, Kunz M, Gilbert F, Ghivizzani S, Göbel S, et al. Indian hedgehog gene transfer is a chondrogenic inducer of human mesenchymal stem cells. Arthritis Res Ther. 2012;14:R168 pubmed publisher..As this study provides evidence for chondrogenic induction of MSC aggregates in vitro via IHH gene delivery, this technology may be efficiently employed for generating cartilaginous repair tissues in vivo. ..
- Monkkonen T, Lewis M. New paradigms for the Hedgehog signaling network in mammary gland development and breast Cancer. Biochim Biophys Acta Rev Cancer. 2017;1868:315-332 pubmed publisher..These new observations offer insight into previously conflicting data, and have bearing on the potential for anti-Hedgehog therapeutics in the treatment of breast cancer. ..
- Cao Z, Dou C, Dong S. Curcumin Inhibits Chondrocyte Hypertrophy of Mesenchymal Stem Cells through IHH and Notch Signaling Pathways. Chem Pharm Bull (Tokyo). 2017;65:762-767 pubmed publisher..Our results indicated curcumin was a potential agent in modulating cartilage homeostasis and maintaining chondrocyte phenotype. ..
- Alonso S, Jones R, Ghiaur G. Retinoic acid, CYP26, and drug resistance in the stem cell niche. Exp Hematol. 2017;54:17-25 pubmed publisher..Bypassing this gatekeeping mechanism holds promise for overcoming drug resistance and improving clinical outcomes in hematological malignancies and cancer in general. ..
- Grausam K, Dooyema S, Bihannic L, Premathilake H, Morrissy A, Forget A, et al. ATOH1 Promotes Leptomeningeal Dissemination and Metastasis of Sonic Hedgehog Subgroup Medulloblastomas. Cancer Res. 2017;77:3766-3777 pubmed publisher..Our work reveals a dynamic ATOH1-driven molecular cascade underlying medulloblastoma metastasis that offers possible therapeutic opportunities. Cancer Res; 77(14); 3766-77. ©2017 AACR. ..
- Ming J, Sun B, Li Z, Lin L, Meng X, Han B, et al. Aspirin inhibits the SHH/GLI1 signaling pathway and sensitizes malignant glioma cells to temozolomide therapy. Aging (Albany NY). 2017;9:1233-1247 pubmed publisher..Impairment of DNA DSBs repair activity might be involved in the route of aspirin-induced chemosensitivity. Combined aspirin with TMZ may be a promising strategy against malignant glioma. ..
- Wang J, Feng J. Signaling Pathways Critical for Tooth Root Formation. J Dent Res. 2017;96:1221-1228 pubmed publisher..Finally, this review includes a list of the various Cre transgenic mouse lines used to achieve tooth root formation-related gene deletion or overexpression, as well as strengths and limitations of each line. ..
- Li J, Zhang L, Xia Q, Fu J, Zhou Z, Lin F. Hedgehog signaling inhibitor GANT61 induces endoplasmic reticulum stress-mediated protective autophagy in hepatic stellate cells. Biochem Biophys Res Commun. 2017;493:487-493 pubmed publisher..Overall, these results demonstrate that simultaneous inhibition of Hh signaling and autophagy or ER stress could be a better way to reduce activated HSCs. ..
- Roberts K, Kershner A, Beachy P. The Stromal Niche for Epithelial Stem Cells: A Template for Regeneration and a Brake on Malignancy. Cancer Cell. 2017;32:404-410 pubmed publisher..Understanding and therapeutic harnessing of the role of stroma in cancer restraint may hinge on our knowledge of the signaling programs elaborated by the stromal niche. ..
- Shao J, Xu L, Chen L, Lu Q, Xie X, Shi W, et al. Arl13b Promotes Gastric Tumorigenesis by Regulating Smo Trafficking and Activation of the Hedgehog Signaling Pathway. Cancer Res. 2017;77:4000-4013 pubmed publisher..Our results show how Arl13b participates in Hh pathway activation in gastric cancer. Cancer Res; 77(15); 4000-13. ©2017 AACR. ..
- Han L, Xu J, Grigg E, Slack M, Chaturvedi P, Jiang R, et al. Osr1 functions downstream of Hedgehog pathway to regulate foregut development. Dev Biol. 2017;427:72-83 pubmed publisher..We conclude that Osr1 is a novel downstream target of HH pathway, required for lung specification, branching morphogenesis and foregut mesenchymal differentiation. ..
- Zheng X, Han H, Liu G, Ma Y, Pan R, Sang L, et al. LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism. EMBO J. 2017;36:3325-3335 pubmed publisher..Taken together, our study not only reveals the mechanism by which YAP reprograms glucose metabolism, but also highlights the therapeutic potential of targeting YAP-BCAR4-glycolysis axis for breast cancer treatment. ..
- Szczepny A, Rogers S, Jayasekara W, Park K, McCloy R, Cochrane C, et al. The role of canonical and non-canonical Hedgehog signaling in tumor progression in a mouse model of small cell lung cancer. Oncogene. 2017;36:5544-5550 pubmed publisher..These results provide strong support for an autocrine, ligand-dependent model of Hh signaling in SCLC pathogenesis, and reveal a novel role for non-canonical Hh signaling through the induction of chromosomal instability...
- Castillo Azofeifa D, Losacco J, Salcedo E, Golden E, Finger T, Barlow L. Sonic hedgehog from both nerves and epithelium is a key trophic factor for taste bud maintenance. Development. 2017;144:3054-3065 pubmed publisher..However, although neurally derived Shh is in part responsible for the dependence of taste cell renewal on gustatory innervation, neurotrophic support of taste buds likely involves a complex set of factors. ..
- Xiao X, Tang J, Peng C, Wang Y, Fu L, Qiu Z, et al. Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling. Mol Cell. 2017;66:154-162.e10 pubmed publisher..Together, the results of our study suggest that Hh signaling transduces to SMO through modulating its cholesterylation and provides a therapeutic opportunity to treat Hh-pathway-related cancers by targeting SMO cholesterylation. ..
- Xu L, Liu H, Yan Z, Sun Z, Luo S, Lu Q. Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells. Int J Oncol. 2017;50:1868-1878 pubmed publisher..These results demonstrate that miR-124 is an important downstream target gene of Hh signaling, and the Gli2/miR-124/AURKA axis is essential for the proliferation and growth of human glioma cells. ..
- Mierzwa A, Sullivan G, Beer L, Ahn S, Armstrong R. Comparison of cortical and white matter traumatic brain injury models reveals differential effects in the subventricular zone and divergent Sonic hedgehog signaling pathways in neuroblasts and oligodendrocyte progenitors. ASN Neuro. 2014;6: pubmed publisher..Notably, cortical versus white matter damage from TBI produced opposite responses of Shh-activated cells within the SVZ. ..
- Dvoriantchikova G, Tao W, Pappas S, Gaidosh G, Tse D, Ivanov D, et al. Molecular Profiling of the Developing Lacrimal Gland Reveals Putative Role of Notch Signaling in Branching Morphogenesis. Invest Ophthalmol Vis Sci. 2017;58:1098-1109 pubmed publisher..Our data also supports the hypothesis that NOTCH signaling regulates branching morphogenesis in the developing lacrimal gland by suppressing cleft formation. ..
- He H, Huang M, Sun S, Wu Y, Lin X. Epithelial heparan sulfate regulates Sonic Hedgehog signaling in lung development. PLoS Genet. 2017;13:e1006992 pubmed publisher..Together, our study highlights the epithelial HS as a key player for dictating SHH signaling critical for lung morphogenesis. ..
- Lu X, Peng Y, Wang C, Yang J, Bao X, Dong Q, et al. Design, synthesis, and biological evaluation of optimized phthalazine derivatives as hedgehog signaling pathway inhibitors. Eur J Med Chem. 2017;138:384-395 pubmed publisher..In vivo efficacy of 23b in a ptch+/-p53-/- mouse medulloblastoma allograft model also indicated encouraging results. ..
- Ehe B, Lamson D, Tarpley M, Onyenwoke R, Graves L, Williams K. Identification of a DYRK1A-mediated phosphorylation site within the nuclear localization sequence of the hedgehog transcription factor GLI1. Biochem Biophys Res Commun. 2017;491:767-772 pubmed publisher..The data described herein provide the first identification of a DYRK1A-mediated site of phosphorylation on GLI1 within its NLS and may serve as a valuable mechanism for further understanding Hh signaling modulation. ..
- Xin M, Zhang L, Wen J, Shen H, Zhao X, Jin Q, et al. Introduction of fluorine to phenyl group of 4-(2-pyrimidinylamino)benzamides leading to a series of potent hedgehog signaling pathway inhibitors. Bioorg Med Chem Lett. 2017;27:3259-3263 pubmed publisher..050nM. This paper finds the introduction of fluorine to the 4-(2-pyrimidinylamino)benzamide scaffold can lead to a novel series of potent Hh signaling pathway inhibitors. ..
- Wadhwa R, Wang X, Baladandayuthapani V, Liu B, Shiozaki H, Shimodaira Y, et al. Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients. Br J Cancer. 2017;117:648-655 pubmed publisher..Our validated data in OC show that nuclear Gli-1 LIs are predictive of pathCR after chemoradiation with desirable sensitivity and specificity. ..
- Liu C, Lan C, Chou J, Tseng T, Liao W. CHSY1 promotes aggressive phenotypes of hepatocellular carcinoma cells via activation of the hedgehog signaling pathway. Cancer Lett. 2017;403:280-288 pubmed publisher..Together, our results indicate that CHSY1 overexpression in HCC contributes to the malignant behaviors in cancer cells, we provide novel insights into the significance of chondroitin sulfate in hedgehog signaling and HCC pathogenesis. ..
- Nakagawa N, Li J, Yabuno Nakagawa K, Eom T, Cowles M, Mapp T, et al. APC sets the Wnt tone necessary for cerebral cortical progenitor development. Genes Dev. 2017;31:1679-1692 pubmed publisher..These results reveal that APC-regulated ?-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. ..
- Almazán Moga A, Zarzosa P, Molist C, Velasco P, Pyczek J, Simon Keller K, et al. Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma: the oncogenic role of the ligands. Br J Cancer. 2017;117:1314-1325 pubmed publisher..Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers. ..