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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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A Cell-Autonomous Oncosuppressive Role of Human RNASET2 Affecting ECM-Mediated Oncogenic Signaling

Francesca Roggiani1, Cristina Riva2, Francesco Raspagliesi3

  • 1Unit of Molecular Therapies, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. francesca.roggiani@istitutotumori.mi.it.

Cancers
|March 1, 2019
PubMed

Insights

Increased RNASET2 expression in epithelial ovarian cancer (EOC) correlates with better survival and altered cell behavior. Targeting activated src may offer a new therapeutic strategy for EOC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • RNASET2, an extracellular ribonuclease, exhibits antitumorigenic properties independent of its catalytic activity.
  • RNASET2 influences immune cell recruitment, responds to cellular stress, and modulates the actin cytoskeleton, impacting extracellular matrix (ECM) interactions.

Purpose of the Study:

  • To investigate the impact of RNASET2 expression modulation on cell phenotype and behavior in epithelial ovarian cancer (EOC) models.
  • To explore the correlation between RNASET2 levels and patient survival and clinical characteristics.

Main Methods:

  • In silico analysis of EOC gene expression datasets (n=392).
  • Immunohistochemical analysis of RNASET2 expression in EOC biopsies (n=101).
  • In vitro studies involving RNASET2 silencing and overexpression in EOC cell models.

Main Results:

  • Higher RNASET2 transcript levels were associated with longer overall survival in EOC patients.
  • RNASET2 expression was heterogeneous in EOC tumors and sometimes localized to the tumor-associated ECM.
  • RNASET2 expression negatively affected EOC cell growth, altered cell phenotype, and decreased src activation upon ECM interaction.

Conclusions:

  • RNASET2 expression is a potential prognostic marker in EOC.
  • Modulating RNASET2 influences EOC cell behavior and interaction with the ECM.
  • Targeting activated src presents a potential therapeutic avenue for RNASET2-expressing EOCs.
Keywords:
RNASET2epithelial ovarian cancerextracellular matrixsrc family kinasessrc kinase

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