Novel role of LLGL2 silencing in autophagy: reversing epithelial-mesenchymal transition in prostate cancer

被引：3

作者：

Hong, Geum-Lan ^{[1
]}

Kim, Kyung-Hyun ^{[1
]}

Kim, Yae-Ji ^{[1
]}

Lee, Hui-Ju ^{[1
]}

Cho, Sung-Pil ^{[1
]}

Han, Seung-Yun ^{[2
]}

Yang, Seung Woo ^{[4
]}

Lee, Jong-Soo ^{[1
]}

Kang, Shin-Kwang ^{[3
]}

Lim, Jae-Sung ^{[4
]}

Jung, Ju-Young ^{[1
]}

机构：

[1] Chungnam Natl Univ, Inst Vet Sci, Coll Vet Med, Dept Vet Med, 99 Daehak Ro, Daejeon 34134, South Korea

[2] Konyang Univ, Coll Med, Dept Anat, Daejeon 35365, South Korea

[3] Chungnam Natl Univ, Chungnam Natl Univ Hosp, Coll Med, Dept Thorac & Cardiovasc Surg, Daejeon 35015, South Korea

[4] Chungnam Natl Univ, Coll Med, Dept Urol, Daejeon 35015, South Korea

来源：

BIOLOGICAL RESEARCH | 2024年 / 57卷 / 01期

关键词：

Autophagy; EMT; LLGL2; Proliferation; Prostate cancer; METASTASIS; EMT; PATHWAY; HUGL-1;

D O I：

10.1186/s40659-024-00499-w

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Purpose Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo.Methods PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model.Results In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and alpha-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition.Conclusion Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.

引用

页数：11