Activin A Signaling Regulates IL13Rα2 Expression to Promote Breast Cancer Metastasis

Frontiers in Oncology
Maria KalliPanagiotis Papageorgis

Abstract

Metastatic dissemination of cancer cells to distal organs is the major cause of death for patients suffering from the aggressive basal-like breast cancer (BLBC) subtype. Recently, we have shown that interleukin 13 receptor alpha 2 (IL13Rα2) is a critical gene that is overexpressed in a subset of BLBC primary tumors associated with poor distant metastasis-free survival (DMFS) and can promote extravasation and metastasis of breast cancer cells to the lungs. However, the upstream signaling mechanisms that promote aberrant IL13Rα2 expression during tumor progression remain unknown. Driven by our previously published gene expression microarray data derived from a well-characterized cell line model for BLBC progression, we show that both Inhibin βA (INHBA) and IL13Rα2 genes exhibit similarly higher expression levels in metastatic compared to non-metastatic cells and that overexpression of both genes predicts worse metastasis-free survival of patients with high grade tumors. Activin A, a member of the TGFβ superfamily comprising two INHBA subunits, has been shown to play context-depended roles in cancer progression. Here, we demonstrate that INHBA depletion downregulates IL13Rα2 expression in metastatic breast cancer cells, whereas tr...Continue Reading

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Citations

Jul 24, 2020·Expert Opinion on Therapeutic Targets·Alexander RiesMichael Grusch
Jul 14, 2020·Bioinformatics·Anja C GumpingerKarsten Borgwardt
Oct 24, 2020·Cancer Immunology Research·Mara De MartinoClaire Vanpouille-Box
Jun 17, 2021·The Journal of International Medical Research·Jia Guo, Yuan Liu
Sep 22, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·R Alejandro Márquez-OrtizDiana M Cittelly

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Methods Mentioned

BETA
PCR
Transfection
immunoprecipitation assay
protein assay
Assay

Software Mentioned

Kaplan Plotter
Image J

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