Amyloid precursor-like protein 2 interacts with claudin-7 and affects ovarian cancer cell survival

Abstract

Aim: In our previous report, we identified roles of CLDN7 in regulation of cell signaling. The goal of this study was to identify proteins interacting with CLDN7 in ovarian cancer. Methods: The yeast two-hybrid system was used to identify proteins directly interacting with CLDN7 and cell survival was tested using colony formation assay. Results: Amyloid precursor-like protein 2 (APLP2) was found directly associated with CLDN7 in ovarian cancer cell line OVCA420. In addition, APLP2 showed increased expression in ovarian cancer cell lines and tumor tissue samples compared with non-neoplastic ovarian tissues. Knockdown of CLDN7 led to increased expression of APLP2 at both the mRNA and protein levels. Knockdown of APLP2 was associated with decreased cell survival in ovarian cancer cells. Conclusion: We show a direct interaction of CLDN7 with APLP2. These findings suggest novel regulatory role for APLP2 in ovarian cancer, a role that appears to be mediated by CLDN7. Lay abstract We conducted this study to find other proteins interacting with CLDN7. CLDN7 is a tight junction protein and increased expression of CLDN7 has been reported in several cancers, including ovarian cancer. Using a yeast two-hybrid approach, we identified amyloid precursor-like protein 2 (APLP2) directly interacting with CLDN7. Like CLDN7, increased levels of APLP2 proteins were found in both ovarian cancer cell lines and ovarian cancer tissue samples. We also identified functional role of APLP2 in ovarian cancer where lowering APLP2 protein levels led to decreased cell survival in ovarian cancer cell line, OVCA420.