Zyxin promotes hepatocellular carcinoma progression via the activation of AKT/mTOR signaling pathway.


Journal

Oncology research
ISSN: 1555-3906
Titre abrégé: Oncol Res
Pays: United States
ID NLM: 9208097

Informations de publication

Date de publication:
2023
Historique:
received: 25 02 2023
accepted: 17 05 2023
medline: 8 8 2023
pubmed: 7 8 2023
entrez: 7 8 2023
Statut: epublish

Résumé

Hepatocellular carcinoma (HCC) is a common malignancy that is driven by multiple genes and pathways. The aim of this study was to investigate the role and specific mechanism of the actin-interacting protein zyxin (ZYX) in HCC. We found that the expression of ZYX was significantly higher in HCC tissues compared to that in normal liver tissues. In addition, overexpression of ZYX in hepatoma cell lines (PLC/PRF/5, HCCLM3) enhanced their proliferation, migration and invasion, whereas ZYX knockdown had the opposite effects (SK HEP-1, Huh-7). Furthermore, the change in the expression levels of ZYX also altered that of proteins related to cell cycle, migration and invasion. Similar results were obtained with xenograft models. The AKT/mTOR signaling pathway is one of the key mediators of cancer development. While ZYX overexpression upregulated the levels of phosphorylated AKT/mTOR proteins, its knockdown had the opposite effect. In addition, the AKT inhibitor MK2206 neutralized the pro-oncogenic effects of ZYX on the HCC cells, whereas the AKT activator SC79 restored the proliferation, migration and invasion of HCC cells with ZYX knockdown. Taken together, ZYX promotes the malignant progression of HCC by activating AKT/mTOR signaling pathway, and is a potential therapeutic target in HCC.

Identifiants

pubmed: 37547758
doi: 10.32604/or.2023.029549
pii: 29549
pmc: PMC10398406
doi:

Substances chimiques

Proto-Oncogene Proteins c-akt EC 2.7.11.1
TOR Serine-Threonine Kinases EC 2.7.11.1
Zyxin 0
ZYX protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

805-817

Informations de copyright

© 2023 Cai et al.

Déclaration de conflit d'intérêts

The authors declare that they have no conflicts of interest to report regarding the present study.

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Auteurs

Tianying Cai (T)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Biobank, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Junjie Bai (J)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Peng Tan (P)

Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Zhiwei Huang (Z)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Chen Liu (C)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Ziming Wu (Z)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Yonglang Cheng (Y)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Tongxi Li (T)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Yifan Chen (Y)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Jian Ruan (J)

Department of Medical Oncology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.

Lin Gao (L)

Department of Health Management, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Yichao DU (Y)

Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Wenguang Fu (W)

Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

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Classifications MeSH