Role of the WNT/β-catenin/ZKSCAN3 Pathway in Regulating Chromosomal Instability in Colon Cancer Cell lines and Tissues.

ABSTRACT: Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) acts as an oncogenic transcription factor in human malignant tumors, including colon and prostate cancer. However, most of the ZKSCAN3-induced carcinogenic mechanisms remain unknown. In this study, we identified ZKSCAN3 as a downstream effector of the oncogenic Wnt/β-catenin signaling pathway, using RNA sequencing and ChIP analyses. Activation of the Wnt pathway by recombinant Wnt gene family proteins or the GSK inhibitor, CHIR 99021 upregulated ZKSCAN3 expression in a β-catenin-dependent manner. Furthermore, ZKSCAN3 upregulation suppressed the expression of the mitotic spindle checkpoint protein, Mitotic Arrest Deficient 2 Like 2 (MAD2L2) by inhibiting its promoter activity and eventually inducing chromosomal instability in colon

SUBMITTER: Cho YE 

PROVIDER: S-EPMC9409321 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature