Rab11-FIP4 interacts with ARF5 to promote cancer stemness in hepatocellular carcinoma

• Song, Feifeng ^[1] ; Zhang, Qi ^[2] ; Lu, Xixuan ^[2] ; Xu, Tong ^[2] ; Hu, Qing ^[2] ; Hu, Xiaoping ^[2] ; Fan, Weijiao ^[3] ; Zhang, Yiwen ^[1] ; Huang, Ping ^[1]
  1. [1] Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital,Afliated People’s Hospital, Hangzhou Medical College, Hangzhou, China; Key Laboratory of Endocrine Gland Diseases of ZhejiangProvince, Hangzhou, China
  2. [2] Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital,Afliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
  3. [3] Cancer Center, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’s Hospital, Afliated People’s Hospital, Hangzhou Medical College, Hangzhou, China

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• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 79, Nº. 4, 2023, págs. 757-770
• Idioma: inglés
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• Resumen

  • Recent studies suggest that Rab11-family interacting proteins (Rab11-FIPs) play an important role in tumorigenesis and progression. Among the Rab11-FIPs, Rab11-FIP4 has been reported to be signifcantly upregulated in various cancers, including hepatocellular carcinoma (HCC). However, the possible efect on HCC stemness and the underlying mechanism has never been characterized. Here, we found that Rab11-FIP4 was dramatically increased in HCC cell lines and tissues, and had a positive correlation with cancer stemness. Functional studies revealed that elevated expression of Rab11-FIP4 in HCC cells signifcantly promoted sphere formation, and enhanced the mRNA and protein levels of stemness-associated markers, ALDH1A1, CD133, NANOG, and OCT4. Conversely, the knockdown of Rab11-FIP4 suppressed the cancer stem cell (CSC)-like characteristics of HCC cells. Moreover, silencing of Rab11-FIP4 obviously increased the sensitivity of HCC cells to sorafenib. Mechanistically, Rab11-FIP4 was shown to interact with ADP-ribosylation factor 5 (ARF5) to infuence cell cycle-related proteins, CDK1/cyclin B, thereby promoting HCC stemness. Taken together, our results uncovered an essential role for Rab11-FIP4 in regulating CSC-like features of HCC cells and identifed Rab11-FIP4 as a potential target for HCC therapy.