Abstract
We investigated the association between c-Src and the progression of hepatocellular carcinoma (HCC) and its underlying mechanisms. The relationship between c-Src expression and the occurrence and development of HCC was explored using GEPIA and further confirmed by western blotting analysis and real-time quantitative PCR. CCK-8, flow cytometry, Transwell, and wound-healing assays were conducted to analyze the effects of c-Src on the growth, cell cycle, apoptosis, migration, and infiltration of HCC cells. Mouse models of transplanted xenogeneic human tumors were constructed to explore the effects of c-Src on HCC tumor growth. Compared with that in adjacent normal liver tissues, the expression level of c-Src in HCC tissues was significantly increased and was negatively correlated with patient survival. These findings are consistent with those in the GEPIA database. Downregulation of c-Src expression can inhibit the growth, infiltration, and migration of HCC cells. c-Src impeded the translocation of YAP from the nucleus to the cytoplasm and promoted Yes-associated protein transcriptional activity. In vivo experiments showed that c-Src inhibition suppressed tumor growth in mice. We found that c-Src can promote the growth and tumorigenesis of HCC cells by activating the Hippo signaling pathway.
Keywords:
Hepatocellular carcinoma; Hippo signaling pathway; Infiltration; Migration; c-Src.
Copyright © 2020 Elsevier Inc. All rights reserved.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Apoptosis / drug effects
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Apoptosis / genetics
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Carcinogenesis / drug effects
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Carcinogenesis / genetics
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Carcinogenesis / metabolism*
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Carcinogenesis / pathology*
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Carcinoma, Hepatocellular / enzymology*
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / pathology*
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Cell Cycle Checkpoints / drug effects
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Cell Cycle Checkpoints / genetics
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Cell Line, Tumor
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Cell Movement / drug effects
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Cell Movement / genetics
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cell Proliferation / drug effects
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Cell Proliferation / genetics
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Gene Expression Regulation, Neoplastic / drug effects
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Hippo Signaling Pathway
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Humans
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Liver Neoplasms / enzymology*
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology*
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Male
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Mice
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Mice, Nude
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Neoplasm Invasiveness
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Prognosis
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Protein Kinase Inhibitors / pharmacology
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
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Proto-Oncogene Proteins pp60(c-src) / genetics
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Proto-Oncogene Proteins pp60(c-src) / metabolism*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Signal Transduction* / drug effects
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic / drug effects
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Up-Regulation / drug effects
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Protein Kinase Inhibitors
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RNA, Messenger
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Transcription Factors
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YAP-Signaling Proteins
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YAP1 protein, human
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Proto-Oncogene Proteins pp60(c-src)
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Protein Serine-Threonine Kinases