SCARA3 inhibits cell proliferation and EMT through AKT signaling pathway in lung cancer

BMC Cancer. 2022 May 16;22(1):552. doi: 10.1186/s12885-022-09631-z.

Abstract

Background: Scavenger receptor class A member 3 (SCARA3) is decreased in prostate cancer and myeloma. However, functions of SCARA3 in various cancers remain unclear. In this study, we tried to evaluate the functional study of SCARA3 in lung cancer.

Methods: The expression level of SCARA3 in the TCGA-database, lung cancer tissue microarray and lung cancer cells and the prognosis of lung cancer patients were measured. Lung cancer tissue microarray was analyzed pathologically using immunohistochemistry, and quantitative analysis of SCARA3 in normal lung cells and lung cancer cells was analyzed using western blot analysis. Survival curves for lung cancer patients were prepared with the Kaplan-Meier method. Migration and invasion of SCARA3 overexpressed lung cancer cells were determined using a Transwell chamber system. Proliferation of lung cancer cells was determined based on cell viability assay using cell culture in vitro and a tumorigenicity model of BALB/C nude mouse in vivo.

Results: The expression of SCARA3 was abnormally reduced in TCGA-database, lung tissue microarray, and various lung cancer cells. However, overexpression of SCARA3 reduced the proliferation of lung cancer. The ability of SCARA3 to inhibit cancer cell proliferation was maintained even in vivo using a mouse xenograft model. In addition, overexpression of SCARA3 reduced migration and invasion ability of lung cancer cells and induced decreases of EMT markers such as β-catenin, vimentin, and MMP9. We aimed to prove the role of SCARA3 in the treatment of Lung cancer, and shown that the expression level of SCARA3 is important in cancer treatment using cisplatin. The enhancement of the effect of cisplatin according to SCARA3 overexpression is via the AKT and JNK pathways.

Conclusions: This study confirmed an abnormal decrease in SCARA3 in lung cancer. Overexpression of SCARA3 potently inhibited tumors in lung cancer and induced apoptosis by increasing sensitivity of lung cancer to cisplatin. These results suggest that SCARA3 is a major biomarker of lung cancer and that the induction of SCARA3 overexpression can indicate an effective treatment.

Keywords: AKT signaling; Lung Cancer; SCARA3; Tumor growth.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Heat-Shock Proteins / metabolism
  • Humans
  • Lung Neoplasms* / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Scavenger Receptors, Class A
  • Signal Transduction

Substances

  • Heat-Shock Proteins
  • SCARA3 protein, human
  • Scavenger Receptors, Class A
  • Proto-Oncogene Proteins c-akt
  • Cisplatin