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Short-Form Ron Promotes Spontaneous Breast Cancer Metastasis through Interaction with Phosphoinositide 3-Kinase

Xuemei Liu1, Ling Zhao, Yoko S Derose

  • 1Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

Genes & Cancer
|December 31, 2011
PubMed

Insights

Short-form Ron (sfRon), an activated receptor tyrosine kinase (RTK) isoform, drives breast cancer aggressiveness and metastasis. Targeting Ron and phosphoinositide 3-kinase (PI3K) offers new therapeutic strategies for this disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Receptor tyrosine kinases (RTKs) are crucial in cancer, with deregulation common in various malignancies.
  • The Ron RTK is linked to tumor aggressiveness, but its precise role in breast cancer progression and metastasis remains unclear.
  • An activated short-form Ron (sfRon) isoform is prevalent in human breast cancers, yet its function is unexplored.

Purpose of the Study:

  • To investigate the role of the short-form Ron (sfRon) isoform in breast cancer aggressiveness, tumor growth, and metastasis.
  • To elucidate the molecular mechanisms by which sfRon contributes to cancer progression.
  • To validate Ron and phosphoinositide 3-kinase (PI3K) as potential therapeutic targets in breast cancer.

Main Methods:

  • Analysis of Ron activity in human breast cancer samples.
  • In vitro and in vivo studies to assess sfRon's impact on tumor growth and metastasis.
  • Mechanistic investigations involving interactions with p85, the regulatory subunit of PI3K.
  • Functional assays with PI3K inhibition and sfRon mutation.

Main Results:

  • sfRon is predominantly expressed and activated in human breast cancers.
  • sfRon expression significantly increased breast cancer aggressiveness, promoting rapid growth and spontaneous metastasis to liver and bone.
  • sfRon facilitates epithelial-mesenchymal transition, invasion, tumor growth, and metastasis via interaction with PI3K/p85.
  • Inhibition of PI3K or disruption of the sfRon-p85 interaction abolished sfRon-mediated tumor promotion.

Conclusions:

  • sfRon is a critical driver of breast cancer aggressiveness and metastasis.
  • The interaction between sfRon and PI3K is essential for its oncogenic functions.
  • Ron and PI3K represent promising therapeutic targets for treating aggressive breast cancer.
Keywords:
PI3KRonbreast cancermetastasisshort-form Ron

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