The GALNT6-LGALS3BP axis promotes breast cancer cell growth
The GALNT6-LGALS3BP axis promotes breast cancer cell growth
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DOI：
10.3892/ijo.2019.4941
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发表时间：
2020-02-01
影响因子：
5.2
通讯作者：
Katagiri, Toyomasa
中科院分区：
文献类型：
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作者：
Kimura, Ryuichiro;Yoshimaru, Tetsuro;Katagiri, Toyomasa
多肽n -乙酰半乳糖氨基转移酶6 （GALNT6）参与o糖基化的起始，据报道，通过与几种底物结合，在乳腺癌的发生中起关键作用；然而，其在促进生长方面的生物学作用尚不清楚。目前的研究表明，GALNT6通过其凝集素半乳糖侧结合可溶性3结合蛋白（LGALS3BP）的o糖基化，在乳腺癌生长中发挥了重要的病理生理作用。LGALS3BP是一种分泌的促进生长的糖蛋白。Cancer Genome Atlas数据分析显示GALNT6的高表达水平与乳腺癌的不良预后显著相关。GALNT6在乳腺癌细胞中o -糖基化LGALS3BP，而通过siRNA敲低GALNT6可抑制LGALS3BP的o -糖基化和分泌，从而抑制乳腺癌细胞的生长。值得注意的是，LGALS3BP在3个位点（T556、T571和S582）被GALNT6潜在地o -糖基化，从而促进自分泌细胞的生长，而在细胞中表达3个Ala取代的LGALS3BP （T556A、T571A和S582A）可显著降低GALNT6依赖性LGALS3BP的o -糖基化和分泌，从而抑制自分泌生长促进作用。本研究结果提示GALNT6-LGALS3BP轴对乳腺癌细胞增殖至关重要，可能是乳腺肿瘤的治疗靶点和生物标志物。
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 galacto-side-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.