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Updated: Jul 24, 2025

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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ROR1-STAT3 signaling contributes to ovarian cancer intra-tumor heterogeneity

Emilia Piki1, Alice Dini1, Juuli Raivola2

  • 1Disease Networks Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90014, Oulu, Finland.

Cell Death Discovery
|July 3, 2023
PubMed

Insights

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) signaling, enhanced by chemotherapy, drives ovarian cancer (OC) progression via STAT3 activation. Targeting ROR1 may overcome OC drug resistance and improve patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Wnt pathway dysregulation is implicated in various cancers, including ovarian cancer (OC).
  • Aberrant expression of the non-canonical Wnt receptor ROR1 is linked to OC progression and drug resistance.
  • The precise molecular mechanisms of ROR1 in OC tumorigenesis remain unclear.

Purpose of the Study:

  • To elucidate the key molecular events mediated by ROR1 in ovarian cancer progression.
  • To investigate the role of ROR1 signaling in response to neoadjuvant chemotherapy.
  • To identify downstream effectors of ROR1 in OC cells.

Main Methods:

  • Analysis of ROR1 expression changes following neoadjuvant chemotherapy.
  • Investigating Wnt5a/ROR1-mediated signaling pathways (AKT/ERK/STAT3) in OC cells.
  • Proteomics and transcriptomics analyses in ROR1-knockdown OC cells and clinical samples.
  • Multiplex immunohistochemistry (mIHC) validation in an independent OC cohort.

Main Results:

  • ROR1 expression is upregulated by neoadjuvant chemotherapy in OC.
  • Wnt5a binding to ROR1 activates oncogenic signaling through AKT/ERK/STAT3.
  • STAT3 is identified as a key downstream effector of ROR1 signaling.
  • ROR1 and STAT3 are co-expressed in both epithelial and stromal cells (including CAFs) of OC tumors.

Conclusions:

  • ROR1 signaling, activated by Wnt5a and enhanced by chemotherapy, promotes OC progression via STAT3.
  • ROR1 and STAT3 are co-expressed in the tumor microenvironment, suggesting a role in stromal-epithelial interactions.
  • ROR1 represents a promising therapeutic target for overcoming OC progression and drug resistance.

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