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Short-form Ron is a novel determinant of ovarian cancer initiation and progression

Katherine M Moxley1, Luyao Wang2, Alana L Welm3

  • 1Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA.

Genes & Cancer
|August 24, 2016
PubMed

Insights

Short-form Ron (sfRon) drives ovarian cancer development and progression. This study reveals sfRon expression in human ovarian cancers, unlike healthy ovaries, highlighting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The full-length Ron receptor tyrosine kinase is implicated in various cancers.
  • The role of the alternative short-form Ron (sfRon) isoform in cancer pathogenesis is largely unknown.

Purpose of the Study:

  • To investigate the role of sfRon in ovarian cancer development and progression.
  • To determine if sfRon is expressed in human ovarian cancer subtypes.

Main Methods:

  • Carcinogen-induced ovarian tumor models in mice.
  • sfRon expression analysis in human ovarian cancer tissues and healthy ovaries.
  • In vitro studies using OVCAR3 cells with and without sfRon introduction.
  • Analysis of cellular pathways including PI3K, PDK1, and MAPK.
  • In vivo tumor growth and metastasis studies.

Main Results:

  • sfRon expression is essential for carcinogen-induced malignant ovarian tumors in mice.
  • sfRon is detected in human ovarian cancer subtypes, including high-grade serous carcinomas, but not in healthy ovaries.
  • Introduction of sfRon into OVCAR3 cells induced epithelial-to-mesenchymal transition, activated PI3K/PDK1, and inhibited MAPK signaling.
  • sfRon promoted an aggressive in vitro phenotype (increased proliferation/migration, decreased adhesion) and enhanced in vivo tumor growth and abdominal spreading.

Conclusions:

  • sfRon plays a critical role in ovarian cancer initiation and progression.
  • sfRon represents a potential therapeutic target for ovarian cancer treatment.
Keywords:
PDK1PI3Khigh-grade serous ovarian cancerovarian cancersfRon

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