2019
DOI: 10.1016/j.ymthe.2019.06.014
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PMPCB Silencing Sensitizes HCC Tumor Cells to Sorafenib Therapy

Abstract: Hepatocellular carcinoma (HCC) tumors invariably develop resistance to cytotoxic and targeted agents, resulting in failed treatment and tumor recurrence. Previous in vivo short hairpin RNA (shRNA) screening evidence revealed mitochondrial-processing peptidase (PMPC) as a leading gene contributing to tumor cell resistance against sorafenib, a multikinase inhibitor used to treat advanced HCC. Here, we investigated the contributory role of the b subunit of PMPC (PMPCB) in sorafenib resistance. Silencing PMPCB inc… Show more

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Cited by 19 publications
(15 citation statements)
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“…The Authors proposed an elegant model where combinatorial strategies against PMPCB / MCL-1 pathway and Raf/Mek/Erk pathway are necessary to promote sorafenib sensitization. 21 Preclinical tools can also be employed to determine novel mechanisms and gene signatures associated with sorafenib resistance. Tovar et al 22 identified the enrichment of tumor-initiating cells (T-ICs) and the activation of fibroblast growth factor ( FGF ) and insulin growth factor ( IGF ) signaling cascades as crucial events leading to sorafenib resistance in a xenograft mouse model.…”
Section: Driver Genes and Sorafenib Resistance In Hccmentioning
confidence: 99%
“…The Authors proposed an elegant model where combinatorial strategies against PMPCB / MCL-1 pathway and Raf/Mek/Erk pathway are necessary to promote sorafenib sensitization. 21 Preclinical tools can also be employed to determine novel mechanisms and gene signatures associated with sorafenib resistance. Tovar et al 22 identified the enrichment of tumor-initiating cells (T-ICs) and the activation of fibroblast growth factor ( FGF ) and insulin growth factor ( IGF ) signaling cascades as crucial events leading to sorafenib resistance in a xenograft mouse model.…”
Section: Driver Genes and Sorafenib Resistance In Hccmentioning
confidence: 99%
“…Mitochondria are also central organelles that regulate cell death such as apoptosis, necrosis, ferroptosis, pyroptosis, and other cell death processes. An increased expression of anti-apoptotic members of the Bcl-2 protein family (Bcl-XL and Mcl-1), which are localized to the mitochondria in HCC cells, can induce resistance to regorafenib and sorafenib ( 27 , 28 ). Resistance to apoptosis also plays a role in the chemoresistance mechanisms of liver cancer cells.…”
Section: Mitochondria Regulate the Progression And Death Of Hepatocellular Carcinomamentioning
confidence: 99%
“…Sorafenib is a broad-spectrum, small molecule inhibitor that can inhibit the expansion, angiogenesis, and apoptosis of many tumor cells. 12 Sorafenib primarily targets serine/threonine kinase, vascular endothelial growth factor receptor (VEGFR), Platelet-derived growth factor receptor beta (PGFRb), Kit, fms-like tyrosine kinase-3 (FLT3), ret proto-oncogene (RET), and other receptor tyrosine kinases to inhibit tumor cell proliferation and angiogenesis, which subsequently inhibits tumor growth. 13 In 602 patients with advanced HCC who had not received systematic treatment before, the median survival time of the sorafenib group was 2.8 months longer than that of placebo group (44%).…”
Section: Sorafenibmentioning
confidence: 99%