Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of General Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Cancer Med. 2024 Nov;13(22):e70267. doi: 10.1002/cam4.70267.
Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) is the enzyme with the activities of methylenetetrahydrofolate dehydrogenase, methylenetetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetase. Our aim was to elucidate the function of MTHFD1 in colorectal cancer (CRC).
In vitro assessments of the proliferation, invasion, and migration abilities of CRC cells were conducted using Immunohistochemistry, Transwell invasion assays, Western blot (WB), and Cell counting Kit-8 assays. WB was also utilized to measure autophagy protein levels and PI3K-AKT-mTOR signaling pathway expression. Furthermore, the role of MTHFD1 was evaluated in vivo by using subcutaneous xenograft tumor models and lateral tail vein metastasis models of human CRC in nude mice.
Overexpression of MTHFD1 promoted the abilities of tumorigenesis and metastasis in CRC in vitro and in vivo and reduced autophagy, attributing to the PI3K-AKT-mTOR signaling pathway in CRC cells. In contrast, the down-regulation of MTHFD1 increased autophagy and suppressed their proliferation, migration, and invasion.
MTHFD1 can modulate the PI3K-AKT-mTOR signaling pathway to suppress autophagy and stimulate tumorigenesis and metastasis.
亚甲基四氢叶酸脱氢酶 1（MTHFD1）是具有亚甲基四氢叶酸脱氢酶、亚甲基四氢叶酸环水解酶和甲酰四氢叶酸合成酶活性的酶。我们的目的是阐明 MTHFD1 在结直肠癌（CRC）中的功能。
通过免疫组织化学、Transwell 侵袭实验、Western blot（WB）和细胞计数试剂盒-8 检测评估 CRC 细胞的增殖、侵袭和迁移能力。WB 还用于测量自噬蛋白水平和 PI3K-AKT-mTOR 信号通路表达。此外，通过使用皮下异种移植肿瘤模型和裸鼠人 CRC 侧尾静脉转移模型来评估 MTHFD1 的作用。
MTHFD1 的过表达促进了 CRC 细胞在体外和体内的致瘤和转移能力，并降低了自噬，这归因于 CRC 细胞中的 PI3K-AKT-mTOR 信号通路。相比之下，下调 MTHFD1 增加了自噬并抑制了它们的增殖、迁移和侵袭。
MTHFD1 可以调节 PI3K-AKT-mTOR 信号通路，抑制自噬并刺激肿瘤发生和转移。
