Research Paper Volume 15, Issue 11 pp 4949—4962
PZR promotes tumorigenicity of lung cancer cells by regulating cell migration and invasion via modulating oxidative stress and cell adhesion
- 1 Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, China
- 2 Department of Laboratory Medicine, Jilin Medical University, Jilin, China
- 3 Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Received: March 14, 2023 Accepted: May 17, 2023 Published: June 6, 2023
https://doi.org/10.18632/aging.204771How to Cite
Copyright: © 2023 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
PZR is a transmembrane glycoprotein encoded by the MPZL1 gene. It serves as a specific binding protein and substrate of tyrosine phosphatase SHP-2 whose mutations cause developmental diseases and cancers. Bioinformatic analyses of cancer gene databases revealed that PZR is overexpressed in lung cancer and correlated with unfavorable prognosis. To investigate the role of PZR in lung cancer, we employed the CRISPR technique to knockout its expression and recombinant lentiviruses to overexpress it in lung adenocarcinoma SPC-A1 cells. While knockout of PZR reduced colony formation, migration, and invasion, overexpression of PZR had the opposite effects. Furthermore, when implanted in immunodeficient mice, PZR-knockout SPC-A1 cells showed suppressed tumor-forming ability. Finally, the underlying molecular mechanism for these functions of PZR is its positive role in activating tyrosine kinases FAK and c-Src and in maintaining the intracellular level of reactive oxygen species (ROS). In conclusion, our data indicated that PZR plays an important role in lung cancer development, and it may serve as a therapeutic target for anti-cancer development and as a biomarker for cancer prognosis.
Abbreviations
PZR: protein zero-related; GETx: Genotype-Tissue Expression; ITIMs: immunoreceptor tyrosine-based inhibition motifs; SHP-2: protein tyrosine phosphatase non-receptor type 11; ROS: reactive oxygen species; NS: Noonan syndrome; LS: LEOPARD syndrome; NSCLC: Non–small-cell lung cancer; SCLC: Small-cell lung cancer; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; GEPIA: Gene Expression Profiling Interactive Analysis; NOD: Nucleotide binding oligomerization domain containing; H/E: Hematoxylin-eosin; DEGs: Differentially expressed genes; DCFH-DA: 2′, 7′-Dichlorodihydrofluorescein diacetate; T-SOD: Total superoxide dismutase; NAC: N-Acetyl-Cysteine.