Chai, Jian Yi and Sugumar, Vaisnevee and Alshawsh, Mohammed Abdullah and Wong, Won Fen and Arya, Aditya and Chong, Pei Pei and Looi, Chung Yeng (2021) The role of smoothened-dependent and -independent hedgehog signaling pathway in tumorigenesis. Biomedicines, 9 (9). ISSN 2227-9059, DOI https://doi.org/10.3390/biomedicines9091188.
Full text not available from this repository.Abstract
The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved among mammals, with crucial roles in regulating embryonic development as well as in cancer initiation and progression. The GLI transcription factors (GLI1, GLI2, and GLI3) are effectors of the Hh pathway and are regulated via Smoothened (SMO)-dependent and SMO-independent mechanisms. The SMO-dependent route involves the common Hh-PTCH-SMO axis, and mutations or transcriptional and epigenetic dysregulation at these levels lead to the constitutive activation of GLI transcription factors. Conversely, the SMO-independent route involves the SMO bypass regulation of GLI transcription factors by external signaling pathways and their interacting proteins or by epigenetic and transcriptional regulation of GLI transcription factors expression. Both routes of GLI activation, when dysregulated, have been heavily implicated in tumorigenesis of many known cancers, making them important targets for cancer treatment. Hence, this review describes the various SMO-dependent and SMO-independent routes of GLI regulation in the tumorigenesis of multiple cancers in order to provide a holistic view of the paradigms of hedgehog signaling networks involving GLI regulation. An in-depth understanding of the complex interplay between GLI and various signaling elements could help inspire new therapeutic breakthroughs for the treatment of Hh-GLI-dependent cancers in the future. Lastly, we have presented an up-to-date summary of the latest findings concerning the use of Hh inhibitors in clinical developmental studies and discussed the challenges, perspectives, and possible directions regarding the use of SMO/GLI inhibitors in clinical settings.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education (MOE) under Fundamental Research Grant Project, FRGS grant[FP103-2019A], Ministry of Higher Education (MOE) under Fundamental Research Grant Project, FRGS grant[FRGS/1/2019/SKK10/UM/02/3] |
| Uncontrolled Keywords: | GLI1 protein;Hedgehog pathway;Mutations;Epigenetic regulation;Glioma-associated oncogene;Noncanonical;Cancer;Clinical trial;Hedgehog inhibitors |
| Subjects: | R Medicine R Medicine > RC Internal medicine R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 19 Aug 2022 07:33 |
| Last Modified: | 19 Aug 2022 07:33 |
| URI: | http://eprints.um.edu.my/id/eprint/28790 |
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