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ROR1 is upregulated in endometrial cancer and represents a novel therapeutic target

Dongli Liu1, Kate Gunther1, Luis A Enriquez1

  • 1Gynaecological Cancer Research Group, Lowy Cancer Research Centre, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.

Scientific Reports
|August 19, 2020
PubMed

Insights

High ROR1 expression correlates with poorer survival in endometrial cancer patients. Silencing ROR1 and overexpressing ROR2 inhibited cancer cell proliferation and migration, suggesting ROR1 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Receptor tyrosine kinases ROR1 and ROR2 are implicated in various cancers.
  • Altered expression of ROR1/2 is observed in multiple tumor types.
  • Previous studies indicate ROR1/2 inhibition reduces tumor proliferation and metastasis.

Purpose of the Study:

  • To investigate the role of ROR1 and ROR2 in endometrial cancer.
  • To correlate ROR1/2 expression with clinicopathological parameters and patient survival.
  • To analyze the in vitro effects of ROR1/2 modulation on endometrial cancer cell behavior.

Main Methods:

  • Immunohistochemistry (IHC) on a cohort of 499 endometrial cancer patients.
  • Kaplan Meier survival analysis (5-year PFS and OS) and Cox multivariate regression.
  • In vitro studies on KLE and MFE-296 endometrial cancer cell lines assessing proliferation, adhesion, migration, and invasion.

Main Results:

  • High ROR1 expression was significantly associated with decreased overall survival (OS) and progression-free survival (PFS).
  • ROR1 silencing and ROR2 overexpression inhibited proliferation in KLE endometrial cancer cells.
  • Modulation of ROR1/2 affected cancer cell migration, with ROR1 silencing decreasing it.

Conclusions:

  • ROR1 plays a significant oncogenic role in endometrial cancer.
  • High ROR1 expression is a negative prognostic marker for endometrial cancer patients.
  • ROR1-targeting therapies warrant further investigation for endometrial cancer treatment.

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