Chromosome instability is one of the hallmarks of cancer. Stromal antigen (STAG) 3 is a core component of the meiosis-specific cohesin complex, which regulates sister chromatid cohesion. Although aberrantly activated genes encoding the cohesin complex have been identified in cancers, little is known about the role of STAG3 in colorectal cancer (CRC). Here, we evaluated the prognostic impact and role of STAG3 in CRC. Analysis of 172 CRC surgical specimens revealed that high STAG3 expression was associated with poor prognosis. STAG3 knockdown inhibited cell migration and increased drug sensitivity to oxaliplatin, 5-fluorouracil, irinotecan hydrochloride hydrate, and BRAF inhibitor in CRC cell lines. The enhanced drug sensitivity was also confirmed in a human organoid established from a CRC specimen. Moreover, suppression of STAG3 increased γH2AX foci. Particularly, in BRAF-mutant CRC cells, STAG3 silencing suppressed the expression of snail family transcriptional repressor 1 and phosphorylation of extracellular signal-regulated kinase via upregulation of dual-specificity phosphatase 6. Our findings suggest that STAG3 is related to poor clinical outcomes and promotes metastasis and chemotherapeutic resistance in CRC. STAG3 may be a novel prognostic marker and potential therapeutic target for CRC.

染色体不稳定是癌症的标志之一。基质抗原（STAG）3是减数分裂特异性黏附素复合物的核心成分，它调节姐妹染色单体的黏附。尽管已在癌症中鉴定出编码黏附蛋白复合物的异常激活基因，但对STAG3在结直肠癌（CRC）中的作用知之甚少。在这里，我们评估了STAG3在CRC中的预后影响和作用。对172例CRC外科手术标本进行的分析显示，STAG3高表达与不良预后有关。STAG3抑制在CRC细胞系中抑制细胞迁移，并增加对奥沙利铂，5-氟尿嘧啶，伊立替康盐酸盐水合物和BRAF抑制剂的药物敏感性。从CRC标本建立的人类器官中也证实了增强的药物敏感性。此外，抑制STAG3增加γH2AX病灶。特别是，在BRAF突变的CRC细胞中，STAG3沉默通过双重特异性磷酸酶6的上调抑制了蜗牛家族转录阻遏物1的表达和细胞外信号调节激酶的磷酸化。我们的发现表明STAG3与不良的临床结局有关并促进转移和化疗耐药性。STAG3可能是CRC的新型预后标志物和潜在治疗靶标。我们的发现表明，STAG3与不良的临床结局有关，并促进CRC的转移和化疗耐药性。STAG3可能是CRC的新型预后标志物和潜在治疗靶标。我们的发现表明，STAG3与不良的临床结局有关，并促进CRC的转移和化疗耐药性。STAG3可能是CRC的新型预后标志物和潜在治疗靶标。