Department of Cardio-Thoracic Surgery, The Affiliated Hospital of South West Medical University, Luzhou, Sichuan, P.R. China.
Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, P.R. China.
Oncol Rep. 2017 Oct;38(4):2369-2377. doi: 10.3892/or.2017.5889. Epub 2017 Aug 8.
Metastasis-associated colon cancer-1 (MACC1) plays an important role in cancer development, but the role and mechansim of MACC1 in squamous cell carcinoma (ESCC) remain unclear. In this study, we found that MACC1 expression was increased in ESCC, and correlated with lymph node metastasis. MACC1 knockdown suppresed ESCC cell proliferation, metastasis and enchanced cell apoptosis. Moreover, MACC1 knockdown inhibited ESCC cell autophagy, and 3-methyladenine was able to rescue MACC1-induced malignant phenotype of ESCC cells. Furthermore, MACC1 knockdown inactivated AMPK-ULK1 signaling pathway, and metformin could rescue MACC1-induced autophagy in ESCC cells. Collectively, this study found that upregulation of MACC1 in ESCC was associated with lymph node metastasis of patients, and MACC1 regulated ESCC cell proliferation, apoptosis, migration and invasion mainly through AMPK-ULK1 induced autophagy.
转移相关结肠癌基因 1（MACC1）在癌症发展中发挥重要作用，但 MACC1 在鳞状细胞癌（ESCC）中的作用和机制尚不清楚。在本研究中，我们发现 MACC1 表达在 ESCC 中增加，并与淋巴结转移相关。MACC1 敲低抑制 ESCC 细胞增殖、转移并增强细胞凋亡。此外，MACC1 敲低抑制 ESCC 细胞自噬，而 3-甲基腺嘌呤能够挽救 MACC1 诱导的 ESCC 细胞恶性表型。此外，MACC1 敲低可使 AMPK-ULK1 信号通路失活，二甲双胍可挽救 MACC1 诱导的 ESCC 细胞自噬。总之，本研究发现 ESCC 中 MACC1 的上调与患者的淋巴结转移有关，MACC1 主要通过 AMPK-ULK1 诱导的自噬调节 ESCC 细胞的增殖、凋亡、迁移和侵袭。
