ANKRD49 promotes the invasion and metastasis of lung adenocarcinoma via a P38/ATF-2 signalling pathway.

Abstract

Lung adenocarcinoma (LUAD) is the most challenging neoplasm to treat in clinical practice. Ankyrin repeat domain 49 protein (ANKRD49) is highly expressed in several carcinomas; however, its pattern of expression and role in LUAD are not known. Tissue microarrays, immunohistochemistry, χ2 test, Spearman correlation analysis, Kaplan-Meier, log-rank test, and Cox's proportional hazard model were used to analyse the clinical cases. The effect of ANKRD49 on the LUAD was investigated using CCK-8, clonal formation, would healing, transwell assays, and nude mice experiment. Expressions of ANKRD49 and its associated downstream protein molecules were verified by real-time PCR, Western blot, immunohistochemistry, and/or immunofluorescence analyses. ANKRD49 expression was highly elevated in LUAD. The survival rate and Cox's modelling analysis indicated that there may be an independent prognostic indicator for LUAD patients. We also found that ANKRD49 promoted the invasion and migration in both in in vitro and in vivo assays, through upregulating matrix metalloproteinase (MMP)-2 and MMP-9 activities via the P38/ATF-2 signalling pathway Our findings suggest that ANKRD49 is a latent biomarker for evaluating LUAD prognosis and promotes the metastasis of A549 cells via upregulation of MMP-2 and MMP-9 in a P38/ATF-2 pathway-dependent manner.

• Authors: Yue-Hua Liu, Meng Yuan, Bai-Xue Xu, Rui Gao, Yu-Jie You, Zhi-Xin Wang, Yong-Cai Zhang, Min Guo, Zhao-Yang Chen, Bao-Feng Yu, Qi-Wei Wang, Hai-Long Wang, Min Pang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 26 Issue 16 Pg. 4401-4415 (08 2022) ISSN: 1582-4934 [Electronic] England
• PMID: 35775112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Activating Transcription Factor 2
• Atf2 protein, mouse
• Muscle Proteins
• ankyrin repeat domain 49 protein, mouse
• Matrix Metalloproteinase 9

Topics

• Activating Transcription Factor 2 (metabolism)
• Adenocarcinoma of Lung (genetics, metabolism)
• Animals
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Lung Neoplasms (pathology)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Nude
• Muscle Proteins (metabolism)
• Signal Transduction