Non-tight junction-related function of claudin-7 in interacting with integrinβ1 to suppress colorectal cancer cell proliferation and migration

Abstract

Wenjing Li,1,2 Chang Xu,1 Kun Wang,1 Yuhan Ding,1 Lei Ding1 1Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Binzhou Medical University Hospital, Binzhou, People’s Republic of China Purpose: We conducted a preliminarily exploration of the role and possible mechanism of the non-tight junction-related function of claudin-7 in the occurrence and development of colorectal cancer.Methods: We selected the colorectal cancer cell line HCT116, constructed a stably transfected claudin-7 knockdown cell line via RNAi and lentiviral infection, and determined the claudin-7 knockdown efficiency. We assessed the biological behavior changes (cell viability, apoptosis, and migration) in the stably transfected HCT116 cells and observed structural changes in the tight junction by transmission electron microscopy. We used a subcutaneous tumor formation model to assess the tumorigenicity of HCT116 cells after claudin-7 knockdown. We assessed the expression and localization of integrinβ1 in the stably transfected cell line by immunofluorescence staining and investigated the interaction between integrinβ1 and claudin-7 by co-immunoprecipitation.Results: After the knockdown of claudin-7 the expression, the viability and migration ability of HCT116 cells increased and apoptosis decreased. Transmission electron microscopy indicated that the intercellular tight junction structure did not change substantially. Furthermore, the tumor growth in nude mice was enhanced. Immunofluorescence staining showed that integrinβ1 and claudin-7 were co-expressed and co-localized on the cell membrane, and immunoprecipitation suggested that claudin-7 interacts with integrinβ1.Conclusion: Claudin-7 may inhibit the proliferation and migration of tumor cells by interacting with integrinβ1, subsequently participating in the development of colorectal cancer. Keywords: Claudin-7, non-tight junction, integrinβ1, colorectal cancer

Keywords

• Claudin-7
• Non-tight junction
• Integrinβ1
• Colorectal cancer