OVOL2 induces autophagy-mediated epithelial-mesenchymal transition by the ERK1/2 MAPK signaling in lung adenocarcinoma

Yali Wang; Lin Shi; Yuchao He; Wenchen Gong; Yanyan Cui; Ran Zuo; Yu Wang; Yi Luo; Liwei Chen; Zhiyong Liu; Peng Chen; Hua Guo

doi:10.1016/j.isci.2024.108873

OVOL2 induces autophagy-mediated epithelial-mesenchymal transition by the ERK1/2 MAPK signaling in lung adenocarcinoma

iScience. 2024 Jan 11;27(2):108873. doi: 10.1016/j.isci.2024.108873. eCollection 2024 Feb 16.

Authors

Yali Wang^{1

2

3

4}, Lin Shi^{1

2

3

5}, Yuchao He^{1

3}, Wenchen Gong^{3

6}, Yanyan Cui⁴, Ran Zuo^{1

2

3}, Yu Wang^{1

2

3}, Yi Luo^{1

3}, Liwei Chen^{1

3}, Zhiyong Liu^{1

3}, Peng Chen^{2

3}, Hua Guo^{1

3}

Affiliations

¹ Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
² Department of Thoracic Oncology, Lung Cancer Diagnosis and Treatment Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
³ National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin 300060, China.
⁴ Department of Oncology, Affiliated Hospital of Chifeng University, Chifeng, Inner Mongolia 024000, China.
⁵ Department of Oncology, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia 010000, China.
⁶ Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

Abstract

Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) plays an important role in malignant tumor progression. Recently, accumulating evidence has shown that autophagy is involved in the regulation of EMT-induced migration. Therefore, the exploration of targets to inhibit EMT by targeting autophagy is important. In this study, we found that OVO-like zinc finger 2 (OVOL2) may be a key target for regulating autophagy-induced EMT. Firstly, we found that OVOL2 expression was dramatically downregulated in LUAD. Low expression of OVOL2 is an indicator of poor prognosis in LUAD. In vitro experiments have shown that downregulation of OVOL2 expression induces EMT, thereby promoting malignant biological behavior, such as proliferation, migration, and invasion of LUAD cells. Interestingly, autophagy is a key step in regulating OVOL2 and inducing EMT. Furthermore, OVOL2 regulates autophagy through the MAPK signaling pathway, ultimately inhibiting the malignant progression of LUAD.

Keywords: Cancer; Molecular biology; Pathophysiology.