TRIP13 promotes metastasis of colorectal cancer regardless of p53 and microsatellite instability status

• DOI: 10.1002/1878-0261.12821
• Publication Date: 2020-10-10T03:35:33Z
• Authors: Sumit Agarwal; Michael Behring; Hyung‐Gyoon Kim; Darshan S. Chandr...; Balabhadrapatruni...; Nirzari Gupta; Prachi Bajpai; Amr Elkholy; Sameer Al Diffalha; Pran K. Datta; Martin J. Heslin; Sooryanarayana Va...; Upender Manne
• Keywords: Microsatellite Instability

Overexpression of TRIP13, a member the AAA‐ATPase family, is linked with various cancers, but its role in metastasis unknown colorectal cancer (CRC). In current study, we investigated TRIP13 experimental and involvement regulation WNT/β‐catenin EGFR signaling pathways. Evaluation formalin‐fixed paraffin‐embedded (FFPE) frozen tissues adenomas CRCs, along their corresponding normal samples, showed that was gradually increased phenotypic expression from adenoma to carcinoma overexpression CRCs independent patient's gender, age, race/ethnicity, pathologic stage, p53 microsatellite instability (MSI) status. Moreover, liver metastases as compared matched adjacent tissues, indicating biological relevance CRC progression metastasis. knockdown impeded colony formation, invasion, motility, spheroid‐forming capacity cells irrespective MSI Furthermore, xenograft studies demonstrated high contributed tumor growth Depletion decreased it interacted tyrosine kinase, FGFR4; this interaction could be essential for activation EGFR‐AKT pathway. addition, Wnt pathway epithelial–mesenchymal transition. Cell‐based assays revealed miR‐192 PNPT1 regulate CRC. Additionally, RNA sequencing identified COL6A3, TREM2, SHC3, KLK7 downstream targets may have functional TRIP13‐mediated summary, our results promotes regardless status, indicated target therapy