Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
CCDC137 affects sorafenib resistance in hepatocellular carcinoma cells by activating the AKT/mTOR signaling pathway.
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Tao Hanchuan, Wang Yu, Wang Fang, Hu Xingchi, Wang Cheng
Аннотация
BACKGROUND: Hepatocellular carcinoma (HCC) is treated with sorafenib as a first-line treatment; however, resistance reduces its clinical effectiveness. It has been demonstrated that CCDC137 influences cell survival and proliferation. However, in HCC, its role in sorafenib resistance has not been thoroughly investigated.
OBJECTIVE: This study examined how CCDC137 makes HCC cells resistant to sorafenib, with a focus on the Akt/mTOR signaling pathway.
METHODS: HCC cell lines resistant to sorafenib (Huh7/sora) were generated by gradually increasing sorafenib concentrations in Huh7 cells. Bioinformatics analysis was performed on the Cancer Genome Atlas (TCGA)-hepatocellular carcinoma (LIHC) dataset and the GSE29721 dataset. The prognostic significance of CCDC137 was verified using Kaplan-Meier survival curves. Using the in vitro cell assays, the consequences of CCDC137 for the migration, apoptosis, invasion, and proliferation of parental HCC cells and sorafenib-resistant cells were assessed. The changes were analyzed using the Western blot test in the AKT/mTOR signaling pathway in resistant cells after CCDC137 knockdown or overexpression.
RESULTS: CCDC137 was significantly elevated in Huh7/sora cells resistant to sorafenib and was linked to a poor outcome for individuals with HCC. CCDC137 knockdown reduced cell viability, induced apoptosis and inhibited migration and invasion in Huh7/sora cells. Conversely, CCDC137 overexpression in Huh7 cells enhanced sorafenib resistance. Mechanistically, CCDC137 activated the Akt/mTOR signaling pathway, AKT inhibition with MK2206 reversed opposition and increased apoptosis in resistant cells.
CONCLUSION: Through triggering the Akt/mTOR signaling pathway, CCDC137 encourages sorafenib resistance in HCC cells, potentially offering a treatment approach to combat sorafenib resistance in HCC cells.
OBJECTIVE: This study examined how CCDC137 makes HCC cells resistant to sorafenib, with a focus on the Akt/mTOR signaling pathway.
METHODS: HCC cell lines resistant to sorafenib (Huh7/sora) were generated by gradually increasing sorafenib concentrations in Huh7 cells. Bioinformatics analysis was performed on the Cancer Genome Atlas (TCGA)-hepatocellular carcinoma (LIHC) dataset and the GSE29721 dataset. The prognostic significance of CCDC137 was verified using Kaplan-Meier survival curves. Using the in vitro cell assays, the consequences of CCDC137 for the migration, apoptosis, invasion, and proliferation of parental HCC cells and sorafenib-resistant cells were assessed. The changes were analyzed using the Western blot test in the AKT/mTOR signaling pathway in resistant cells after CCDC137 knockdown or overexpression.
RESULTS: CCDC137 was significantly elevated in Huh7/sora cells resistant to sorafenib and was linked to a poor outcome for individuals with HCC. CCDC137 knockdown reduced cell viability, induced apoptosis and inhibited migration and invasion in Huh7/sora cells. Conversely, CCDC137 overexpression in Huh7 cells enhanced sorafenib resistance. Mechanistically, CCDC137 activated the Akt/mTOR signaling pathway, AKT inhibition with MK2206 reversed opposition and increased apoptosis in resistant cells.
CONCLUSION: Through triggering the Akt/mTOR signaling pathway, CCDC137 encourages sorafenib resistance in HCC cells, potentially offering a treatment approach to combat sorafenib resistance in HCC cells.