Stratifin promotes the malignant progression of HCC via binding and hyperactivating AKT signaling

Rong Li; Xijing Yan; Wenhui Zhong; Jun Zheng; Xuejiao Li; Jinliang Liang; Zhongying Hu; Huanyi Liu; Guihua Chen; Yang Yang; Jianwei Zhang; Enze Qu; Wei Liu

doi:10.1016/j.canlet.2024.216761

Stratifin promotes the malignant progression of HCC via binding and hyperactivating AKT signaling

Cancer Lett. 2024 Mar 13:592:216761. doi: 10.1016/j.canlet.2024.216761. Online ahead of print.

Authors

Rong Li¹, Xijing Yan², Wenhui Zhong³, Jun Zheng², Xuejiao Li⁴, Jinliang Liang⁴, Zhongying Hu⁴, Huanyi Liu⁴, Guihua Chen⁵, Yang Yang⁶, Jianwei Zhang⁷, Enze Qu⁸, Wei Liu⁹

Affiliations

¹ Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, 510630, China; Guangdong Province Engineering Laboratory for Transplantation Medicine, Organ Transplantation Research Center of Guangdong Province, Guangzhou, 510630, China.
² Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
³ Department of Pancreatic and Gastric Surgery, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
⁴ Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, 510630, China.
⁵ Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, 510630, China; Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
⁶ Guangdong Province Engineering Laboratory for Transplantation Medicine, Organ Transplantation Research Center of Guangdong Province, Guangzhou, 510630, China; Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. Electronic address: yysysu@163.com.
⁷ Department of Pancreatic and Gastric Surgery, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address: panchutong@163.com.
⁸ Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China. Electronic address: quenz@mail.sysu.edu.cn.
⁹ Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, 510630, China; Guangdong Province Engineering Laboratory for Transplantation Medicine, Organ Transplantation Research Center of Guangdong Province, Guangzhou, 510630, China. Electronic address: lwei6@mail.sysu.edu.cn.

PMID: 38490326
DOI: 10.1016/j.canlet.2024.216761

Abstract

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with limited treatment options and poor prognosis. In this study, we reveal the pivotal role of Stratifin (SFN), also recognized as 14-3-3σ, in driving HCC progression. Our investigation underscores a substantial upregulation of SFN within HCC tissues, manifesting a significant association with worse prognostic outcomes among HCC patients. In vitro and in vivo experiments reveal that SFN overexpression significantly amplifies proliferation, mitigates sorafenib-induced effects on HCC cells, and enhances tumorigenesis. While SFN silencing exerts converse effects on HCC progression. Additionally, we unveil a critical interaction between SFN and AKT, where SFN boosts AKT kinase activity by disrupting the binding of PHLPP2 and AKT, thereby intensifying the malignant progression of HCC cells. In conclusion, this study identifies the oncogenic role of SFN and elucidates the regulatory mechanism of the SFN/AKT axis in HCC, which may provide valuable insights into the mechanisms of HCC progression and potential targets for therapeutic intervention.

Keywords: AKT; Hepatocellular carcinoma; Malignant progression; Stratifin; Therapeutic target.