Zang Yi, Zhu Lei, Li Tong, Wang Qi, Li Juanjuan, Qian Yuting, Wei Lumin, Xie Mingping, Tang Wen-Hao, Liu Xu, Zhu Ying, Wang Lifu
Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Gastroenterol Res Pract. 2018 Oct 2;2018:2626545. doi: 10.1155/2018/2626545. eCollection 2018.
The EI24 autophagy-associated transmembrane protein is frequently associated with tumor growth and patient survival. In the present study, we found that EI24 was downregulated in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues and was associated with cancer cell differentiation. Overexpression of EI24 suppressed cancer cell growth and and induced cell cycle S phase arrest, with no impact on caspase-dependent apoptosis. EI24 overexpression also resulted in reduced c-Myc expression, an oncogene in PDAC, accompanied with increased LC3B-II formation, increased Beclin-1, and diminished p62. Together, we propose that EI24 suppresses cell proliferation and prompts cell cycle arrest in pancreatic cancer cells by activating the autophagic lysosomal degradation of c-Myc. Our results suggest a potential mechanism underlying the antitumor effects of EI24 in PDAC and provide insight into the crosstalk between autophagy and cell proliferation involving a possible EI24/Beclin-1/p62/c-Myc signaling pathway.
EI24自噬相关跨膜蛋白常与肿瘤生长及患者生存相关。在本研究中，我们发现与相邻正常组织相比，EI24在胰腺导管腺癌（PDAC）组织中表达下调，且与癌细胞分化相关。EI24的过表达抑制癌细胞生长并诱导细胞周期S期阻滞，对依赖半胱天冬酶的凋亡无影响。EI24的过表达还导致PDAC中的癌基因c-Myc表达降低，同时伴有LC3B-II形成增加、Beclin-1增加以及p62减少。总之，我们提出EI24通过激活c-Myc的自噬溶酶体降解来抑制胰腺癌细胞的增殖并促使细胞周期阻滞。我们的结果提示了EI24在PDAC中抗肿瘤作用的潜在机制，并为涉及可能的EI24/Beclin-1/p62/c-Myc信号通路的自噬与细胞增殖之间的相互作用提供了见解。
