IQGAP1 promotes anoikis resistance and metastasis through Rac1-dependent ROS accumulation and activation of Src/FAK signalling in hepatocellular carcinoma.

Abstract

BACKGROUND:

Hepatitis B virus (HBV) has a crucial role in the progression of hepatocellular carcinoma (HCC). Tumour cells must develop anoikis resistance in order to survive before metastasis. This study aimed to investigate the mechanism of IQGAP1 in HBV-mediated anoikis evasion and metastasis in HCC cells.

METHODS:

IQGAP1 expression was detected by immunohistochemistry, real-time PCR and immunoblot analysis. Lentiviral-mediated stable upregulation or knockdown of IGAQP1, immunoprecipitation, etc. were used in function and mechanism study.

RESULTS:

IQGAP1 was markedly upregulated in HBV-positive compared with HBV-negative HCC cells and tissues. IQGAP1 was positively correlated to poor prognosis of HBV-associated HCC patients. IQGAP1 overexpression significantly enhanced the anchorage-independent growth and metastasis, whereas IQGAP1-deficient HCC cells are more sensitive to anoikis. Mechanistically, we found that HBV-induced ROS enhanced the association of IQGAP1 and Rac1 that activated Rac1, leading to phosphorylation of Src/FAK pathway. Antioxidants efficiently inhibited IQGAP1-mediated anoikis resistance and metastasis.

CONCLUSIONS:

Our study indicated an important mechanism by which upregulated IQGAP1 by HBV promoted anoikis resistance, migration and invasion of HCC cells through Rac1-dependent ROS accumulation and activation of Src/FAK signalling, suggesting IQGAP1 as a prognostic indicator and a novel therapeutic target in HCC patients with HBV infection.

• Authors: Chun-Fen Mo, Jun Li, Shu-Xia Yang, Hui-Jie Guo, Yang Liu, Xing-Yan Luo, Yan-Tang Wang, Min-Hui Li, Jing-Yi Li, Qiang Zou
• Journal: British journal of cancer (Br J Cancer) Vol. 123 Issue 7 Pg. 1154-1163 (09 2020) ISSN: 1532-1827 [Electronic] England
• PMID: 32632148 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IQ motif containing GTPase activating protein 1
• RAC1 protein, human
• Reactive Oxygen Species
• ras GTPase-Activating Proteins
• Focal Adhesion Kinase 1
• PTK2 protein, human
• src-Family Kinases
• rac1 GTP-Binding Protein

Topics

• Animals
• Anoikis
• Carcinoma, Hepatocellular (pathology)
• Cell Line, Tumor
• Female
• Focal Adhesion Kinase 1 (physiology)
• Hepatitis B (complications)
• Humans
• Liver Neoplasms (pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Metastasis
• Reactive Oxygen Species (metabolism)
• Signal Transduction (physiology)
• rac1 GTP-Binding Protein (physiology)
• ras GTPase-Activating Proteins (physiology)
• src-Family Kinases (physiology)