The GALNT6‑LGALS3BP axis promotes breast cancer cell growth

Abstract

Polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6), which is involved in the initiation of O-glycosylation, has been reported to play crucial roles in mammary carcinogenesis through binding to several substrates; however, its biological roles in mediating growth-promoting effects remain unknown. The present study demonstrated a crucial pathophysiological role of GALNT6 through its O-glycosylation of lectin galactoside-binding soluble 3 binding protein (LGALS3BP), a secreted growth-promoting glycoprotein, in breast cancer growth. The Cancer Genome Atlas data analysis revealed that high expression levels of GALNT6 were significantly associated with poor prognosis of breast cancer. GALNT6 O-glycosylated LGALS3BP in breast cancer cells, whereas knockdown of GALNT6 by siRNA led to the inhibition of both the O-glycosylation and secretion of LGALS3BP, resulting in the suppression of breast cancer cell growth. Notably, LGALS3BP is potentially O-glycosylated at three sites (T556, T571 and S582) by GALNT6, thereby promoting autocrine cell growth, whereas the expression of LGALS3BP with three Ala substitutions (T556A, T571A and S582A) in cells drastically reduced GALNT6-dependent LGALS3BP O-glycosylation and secretion, resulting in suppression of autocrine growth-promoting effect. The findings of the present study suggest that the GALNT6-LGALS3BP axis is crucial for breast cancer cell proliferation and may be a therapeutic target and biomarker for mammary tumors.