TJP1, a Membrane-Expressed Protein, is a Potential Therapeutic and Prognostic Target for Lung Cancer

Abstract

Objective: Lung cancer is a malignant tumor with the highest mortality rate in the world. It is necessary to develop effective biomarkers for diagnosis or prognostic treatment to improve the survival rate of patients. In this prospective study, we identified a membrane-expressed protein Tight Junction Protein 1 (TJP1), which is an ideal therapeutic target for lung cancer, and demonstrated its role in invasion, migration, and proliferation of lung cancer. Methods: High-throughput monoclonal antibody microarrays were used to screen for differential expression of monoclonal antibodies (mAbs) in lung cancer and normal lung tissue. Differentially expressed antibodies were used to immunoprecipitate their cellular targets to be identified by mass spectrometry. The identified target TJP1 was knocked down to observe the effect of reduced gene expression on lung cancer cell function. Immunohistochemistry on human tumor tissues and The Cancer Genome Atlas (TCGA) database was used to explore the relationship between TJP1 expression in multiple cancer types and patient prognosis. Results: The antibody CL007473 was overexpressed in tumor tissue and its target protein was identified by mass spectrometry and immunofluorescence as TJP1, a membrane-expressed protein. Knockdown of TJP1 in lung cancer cell lines showed that reduced expression of TJP1 could inhibit the invasion and migration of lung cancer cells and inhibit the proliferation of cancer cells, suggesting that membrane-expressed protein TJP1 may be used as a therapeutic target for lung cancer. TCGA database analysis showed that TJP1 was highly expressed in pancreatic cancer (PAAD) tissues compared with normal tissues, and low expression was more beneficial to the prognosis and survival of PAAD patients. Conclusion: Membrane-expressed protein TJP1 may be a good therapeutic and prognostic target for lung cancer and has the potential to be a prognostic biomarker in pancreatic cancer.

Unveiling the Influence of Tumor Microenvironment and Spatial Heterogeneity on Temozolomide Resistance in Glioblastoma Using an Advanced Human In Vitro Model of the Blood‐Brain Barrier and Glioblastoma

“…TJP1 (Tight junction protein 1 or Zonula occluden 1) forms part of the complex at the cell‐cell junction of endothelial cells within the BBB that mediate permeability, [ 58 ] but has also been shown to promote tumor cell invasion and angiogenesis in cancers of epithelial origin. [ 59,60 ] HOMER3 is a scaffold protein important for the development of the nervous system, by contributing to calcium signaling and interacting with transcription factors, [ 61 ] and is particularly enriched in the blood vessels of the developing brain. [ 62 ] More recently, it has been described to promote tumor invasion and proliferation in aggressive gliomas and bladder cancer.…”

The Role of Methylation in Chronic Lymphocytic Leukemia and Its Prognostic and Therapeutic Impacts in the Disease: A Systematic Review

“…Reactive oxygen species signaling. Nitrous oxide signaling THBS1 promoter methylation was detected in 50% of the samples while in normal samples, gene promoters were mainly unmethylated [51,150,151] TJP1 Immune cell transmigration VCAM-1/CD106 signaling gene expression (transcription); MAGuK tumor suppressor pathway TJP1expression was reduced in patients with hypermethylated promoter regions and hypomethylated body regions [37,152] CLL: chronic lymphocytic leukemia, Ref. : reference, SERPINB5: serine protease inhibitor B5, THBS1: thrombospondin-1, TJP1: tight junction protein 1, Tap63: tumor protein P63, VCAM-1: vascular cell adhesion protein 1, CD106: cluster of diferentiation 106, MAGuK: membrane-associated guanylate kinases, IGVH: immunoglobulin variable heavy chain gene.…”