Ras suppressor-1 (RSU1) exerts a tumor suppressive role with prognostic significance in lung adenocarcinoma

Clin Exp Med. 2023 Jul;23(3):871-885. doi: 10.1007/s10238-022-00847-8. Epub 2022 Jun 21.

Abstract

Ras suppressor-1 (RSU1), originally described as a suppressor of Ras oncogenic transformation, localizes to focal adhesions interacting with the ILK-PINCH-PARVIN (IPP) complex that exerts a well-established oncogenic role in cancer. However, RSU1 implication in lung cancer is currently unknown. Our study aims to address the role of RSU1 in lung adenocarcinoma (LUADC). We here show that RSU1 protein expression by immunohistochemistry is downregulated in LUADC human tissue samples and represents a significant prognostic indicator. In silico analysis of gene chip and RNA seq data validated our findings. Depletion of RSU1 by siRNA in lung cancer cells promotes anchorage-independent cell growth, cell motility and epithelial to mesenchymal transition (EMT). Silencing of RSU1 also alters IPP complex expression in lung cancer cells. The p29 RSU1 truncated isoform is detected in lung cancer cells, and its expression is downregulated upon RSU1 silencing, whereas it is overexpressed upon ILK overexpression. These findings suggest that RSU1 exerts a tumor suppressive role with prognostic significance in LUADC.

Keywords: EMT; Lung adenocarcinoma; Prognosis; Ras suppressor 1; ΙPP complex.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Prognosis
  • Transcription Factors / metabolism

Substances

  • RSU1 protein, human
  • Transcription Factors