ROR1 potentiates FGFR signaling in basal-like breast cancer

Gaurav Pandey, Nicholas Borcherding, Ryan Kolb, Paige Kluz, Wei Li, Sonia Sugg, Jun Zhang, Dazhi A. Lai, Weizhou Zhang

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Among all breast cancer types, basal-like breast cancer (BLBC) represents an aggressive subtype that lacks targeted therapy. We and others have found that receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in BLBC and other types of cancer and that ROR1 is significantly correlated with patient prognosis. In addition, using primary patient-derived xenografts (PDXs) and ROR1-knockout BLBC cells, we found that ROR1+ cells form tumors in immunodeficient mice. We developed an anti-ROR1 immunotoxin and found that targeting ROR1 significantly kills ROR1+ cancer cells and slows down tumor growth in ROR1+ xenografts. Our bioinformatics analysis revealed that ROR1 expression is commonly associated with the activation of FGFR-mediated signaling pathway. Further biochemical analysis confirmed that ROR1 stabilized FGFR expression at the posttranslational level by preventing its degradation. CRISPR/Cas9-mediated ROR1 knockout significantly reduced cancer cell invasion at cellular levels by lowering FGFR protein and consequent inactivation of AKT. Our results identified a novel signaling regulation from ROR1 to FGFR and further confirm that ROR1 is a potential therapeutic target for ROR1+ BLBC cells.

Original languageEnglish
Article number718
JournalCancers
Volume11
Issue number5
DOIs
StatePublished - May 2019
Externally publishedYes

Keywords

  • Breast cancer
  • Cancer therapy
  • FGFR signaling
  • ROR1

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