Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
Mol Oncol. 2023 Jan;17(1):119-133. doi: 10.1002/1878-0261.13347. Epub 2022 Dec 5.
GalNAc-type O-glycosylation and its initiating GalNAc transferases (GALNTs) play crucial roles in a wide range of cellular behaviors. Among 20 GALNT members, GALNT2 is consistently associated with poor survival of patients with colorectal cancer in public databases. However, its clinicopathological significance in colorectal cancer remains unclear. In this study, immunohistochemistry showed that GALNT2 was overexpressed in colorectal tumors compared with the adjacent nontumor tissues. GALNT2 overexpression was associated with poor survival of colorectal cancer patients. Forced expression of GALNT2 promoted migration and invasion as well as peritoneal metastasis of colorectal cancer cells. In contrast, GALNT2 knockdown with siRNAs or knockout with CRISPR/Cas9 system suppressed these malignant properties. Interestingly, we found that GALNT2 modified O-glycans on AXL and determined AXL levels via the proteasome-dependent pathway. In addition, the GALNT2-promoted invasiveness was significantly reversed by AXL siRNAs. These findings suggest that GALNT2 promotes colorectal cancer invasion at least partly through AXL.
GalNAc 型 O-糖基化及其起始 GalNAc 转移酶 (GALNTs) 在广泛的细胞行为中起着至关重要的作用。在 20 种 GALNT 成员中，GALNT2 在公共数据库中与结直肠癌患者的不良生存始终相关。然而，其在结直肠癌中的临床病理意义尚不清楚。在这项研究中，免疫组织化学显示，与相邻非肿瘤组织相比，GALNT2 在结直肠肿瘤中过表达。GALNT2 的过表达与结直肠癌患者的不良生存相关。过表达 GALNT2 可促进结直肠癌细胞的迁移和侵袭以及腹膜转移。相比之下，用 siRNAs 敲低 GALNT2 或用 CRISPR/Cas9 系统敲除 GALNT2 可抑制这些恶性特性。有趣的是，我们发现 GALNT2 修饰了 AXL 上的 O-聚糖，并通过蛋白酶体依赖性途径确定了 AXL 的水平。此外，AXL siRNAs 显著逆转了 GALNT2 促进的侵袭性。这些发现表明，GALNT2 至少部分通过 AXL 促进结直肠癌的侵袭。
