ANKRD1 suppresses cell proliferation and migration by regulating Wnt/β-catenin signaling in triple-negative breast cancer

Abstract

Ankyrin repeat domain 1 (ANKRD1) is a functionally pleiotropic protein and is known to function as a transcription cofactor. It is highly expressed in skeletal muscle and heart, but its function in breast cancer is not well characterized. I found that ANKRD1 is negatively correlated with a poor prognosis in breast cancer. In addition, the expression of ANKRD1 was lower in the tumor than in normal breast and was found to be the lowest in the metastatic breast tumor. To investigate the role of ANKRD1 in breast cancer, I established ANKRD1 overexpression and knockdown cell lines using human triple-negative breast cancer (TNBC) cell lines. Expression of ANKRD1 decreased cell proliferation, colony formation, in vivo tumor growth, wound healing, and migration. I also found that ANKRD1 expression downregulates β-catenin, which is known to play an important role in cell growth and epithelial-mesenchymal transition. Downregulation of β-catenin protein expression and transcriptional activity reduces the expression of β-catenin target genes in ANKRD1 overexpression cells. I also checked for Wnt signaling activation to determine β-catenin upstream signaling and found reduction of phosphorylated LRP6 and upregulation of DKK1 expression in ANKRD1 overexpression cell lines. Based on these data, I propose that ANKRD1 may act as a tumor suppressor by regulating Wnt/β-catenin signaling in TNBC.