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Title: GASC1 promotes hepatocellular carcinoma progression by inhibiting the degradation of ROCK2
Authors: Shao, Na
Cheng, Jiamin
Huang, Hong
Gong, Xiaoshan
Lu, Yongling
Idris, Muhammad
Peng, Xu
Ong, Belinda X.
Zhang, Qiongyi
Xu, Feng 
Liu, Chungang
Issue Date: 1-Mar-2021
Publisher: Springer Nature
Citation: Shao, Na, Cheng, Jiamin, Huang, Hong, Gong, Xiaoshan, Lu, Yongling, Idris, Muhammad, Peng, Xu, Ong, Belinda X., Zhang, Qiongyi, Xu, Feng, Liu, Chungang (2021-03-01). GASC1 promotes hepatocellular carcinoma progression by inhibiting the degradation of ROCK2. Cell Death and Disease 12 (3) : 253. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Hepatocellular carcinoma (HCC) is a devastating malignancy without targeted therapeutic options. Our results indicated that the histone demethylase GASC1 signature is associated with later tumor stage and poorer survival in HCC patients. GASC1 depletion led to diminished HCC proliferation and tumor growth. A distinct heterogeneity in GASC1 levels was observed among HCC cell populations, predicting their inherent high or low tumor-initiating capacity. Mechanistically, GASC1 is involved in the regulation of several components of the Rho-GTPase signaling pathway including its downstream target ROCK2. GASC1 demethylase activity ensured the transcriptional repression of FBXO42, a ROCK2 protein-ubiquitin ligase, thereby inhibiting ROCK2 degradation via K63-linked poly-ubiquitination. Treatment with the GASC1 inhibitor SD70 impaired the growth of both HCC cell lines and xenografts in mice, sensitizing them to standard-of-care chemotherapy. This work identifies GASC1 as a malignant-cell-selective target in HCC, and GASC1-specific therapeutics represent promising candidates for new treatment options to control this malignancy. © 2021, The Author(s).
Source Title: Cell Death and Disease
ISSN: 2041-4889
DOI: 10.1038/s41419-021-03550-w
Rights: Attribution 4.0 International
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