2. Academic Validation
  3. Septin11 promotes hepatocellular carcinoma cell motility by activating RhoA to regulate cytoskeleton and cell adhesion

Septin11 promotes hepatocellular carcinoma cell motility by activating RhoA to regulate cytoskeleton and cell adhesion

  • Cell Death Dis. 2023 Apr 20;14(4):280. doi: 10.1038/s41419-023-05726-y.
Lisheng Fu # 1,  Xiaoyan Wang # 2,  Ying Yang 1,  MeiHua Chen 3,  Adilijiang Kuerban 4,  Haojie Liu 3,  Yiwei Dong 1,  QianQian Cai 5 6,  Mingzhe Ma 7,  XingZhong Wu 8
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Department of Cardiology of Huadong Hospital Affiliated to Fudan University, Fudan University, 200032, Shanghai, People's Republic of China.
  • 2 Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, 200032, Shanghai, People's Republic of China.
  • 3 NHC Key Laboratory of Glycoconjugates, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032, Shanghai, People's Republic of China.
  • 4 Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Fudan University, 200040, Shanghai, People's Republic of China.
  • 5 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Department of Cardiology of Huadong Hospital Affiliated to Fudan University, Fudan University, 200032, Shanghai, People's Republic of China. cindy5520@126.com.
  • 6 Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 201318, Shanghai, China. cindy5520@126.com.
  • 7 Department of Gastric Surgery, Shanghai Cancer Center of Fudan University, 200032, Shanghai, People's Republic of China. mmz666@163.com.
  • 8 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, and Department of Cardiology of Huadong Hospital Affiliated to Fudan University, Fudan University, 200032, Shanghai, People's Republic of China. xz_wu@shmu.edu.cn.
  • # Contributed equally.
PMID: 37080972 DOI: 10.1038/s41419-023-05726-y
Abstract

Septins as GTPases in the Cytoskeleton, are linked to a broad spectrum of cellular functions, including cell migration and the progression of hepatocellular carcinoma (HCC). However, roles of SEPT11, the new member of septin, have been hardly understood in HCC. In the study, the clinical significance and biological function of SEPT11 in HCC was explored. SEPT11 was screened out by combining ATAC-seq with mRNA-seq. Role of SEPT11 in HCC was further investigated by using overexpression, shRNA and CRISPR/Cas9-mediated SEPT11-knockout cells or in vivo models. We found RNA-seq and ATAC-seq highlights LncRNA AY927503 (AY) induced SEPT11 transcription, resulting in Rho GTPase activation and Cytoskeleton actin aggregation. The GTP-binding protein SEPT11 is thus considered, as a downstream factor of AY, highly expressed in various tumors, including HCC, and associated with poor prognosis of the patients. In vitro, SEPT11 overexpression promotes the migration and invasion of HCC cells, while SEPT11-knockout inhibits migration and invasion. In vivo, SEPT11-overexpressed HCC cells show high metastasis incidents but don't significantly affect proliferation. Meanwhile, we found SEPT11 targets RhoA, thereby regulating Cytoskeleton rearrangement and abnormal cell adhesion through ROCK1/cofilin and FAK/paxillin signaling pathways, promoting invasion and migration of HCC. Further, we found SEPT11 facilitates the binding of GEF-H1 to RhoA, which enhances the activity of RhoA. Overall, our study confirmed function of SEPT11 in promoting metastasis in HCC, and preliminarily explored its related molecular mechanism. SEPT11 acts as an oncogene in HCC, also draws further interest regarding its clinical application as a potential therapeutic target.

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