Although synaptotagmin 1 (SYT1) has been identified participating in a variety of cancers, its role in colorectal cancer (CRC) remains an enigma. This study aimed to demonstrate the effect of SYT1 on CRC metastasis and the underlying mechanism. We first found that SYT1 expressions in CRC tissues were lower than in normal colorectal tissues from the CRC database and collected CRC patients. In addition to this, SYT1 expression was also lower in CRC cell lines than in the normal colorectal cell line. SYT1 expression was downregulated by TGF-β (an EMT mediator) in CRC cell lines. In vitro, SYT1 overexpression repressed pseudopodial formation and reduced cell migration and invasion of CRC cells. SYT1 overexpression also suppressed CRC metastasis in tumor-bearing nude mice in vivo. Moreover, SYT1 overexpression promoted the dephosphorylation of ERK1/2 and downregulated the expressions of Slug and Vimentin, two proteins tightly associated with EMT in tumor metastasis. In conclusion, SYT1 expression is downregulated in CRC. Overexpression of SYT1 suppresses CRC cell migration, invasion, and metastasis by inhibiting ERK/MAPK signaling-mediated CRC cell pseudopodial formation. The study suggests that SYT1 is a suppressor of CRC and may have the potential to be a therapeutic target for CRC.
尽管突触结合蛋白1（SYT1）已被证实参与多种癌症的发生发展，但其在结直肠癌（CRC）中的作用机制尚不明确。本研究旨在阐明SYT1对结直肠癌转移的影响及其潜在机制。通过分析结直肠癌数据库及临床样本，我们首次发现结直肠癌组织中SYT1的表达水平低于正常结直肠组织。此外，结直肠癌细胞系中SYT1的表达也显著低于正常结直肠细胞系。在结直肠癌细胞中，TGF-β（上皮间质转化的关键调控因子）可下调SYT1的表达。体外实验表明，过表达SYT1能抑制结直肠癌细胞的伪足形成，并降低其迁移和侵袭能力。在荷瘤裸鼠体内实验中，SYT1过表达同样能抑制结直肠癌的转移。机制研究发现，SYT1过表达可促进ERK1/2的去磷酸化，并下调与肿瘤转移过程中上皮间质转化密切相关的Slug和Vimentin蛋白表达。综上所述，SYT1在结直肠癌中表达下调，其过表达通过抑制ERK/MAPK信号通路介导的伪足形成，从而抑制结直肠癌细胞的迁移、侵袭和转移。本研究提示SYT1可作为结直肠癌的抑制因子，并具有成为结直肠癌治疗靶点的潜力。
肿瘤(癌症)患者之家