Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression

Amira F. Mahdi, Joanne Nolan, Ruth O’Connor, Aoife J. Lowery, Joanna M. Allardyce, Patrick A. Kiely, Kieran McGourty

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: The extracellular matrix (ECM) has been heavily implicated in the development and progression of cancer. We have previously shown that Annexin A2 is integral in the migration and invasion of breast cancer cells and in the clinical progression of ER-negative breast cancer, processes which are highly influenced by the surrounding tumor microenvironment and ECM. Methods: We investigated how modulations of the ECM may affect the role of Annexin A2 in MDA-MB-231 breast cancer cells using western blotting, immunofluorescent confocal microscopy and immuno-precipitation mass spectrometry techniques. Results: We have shown that the presence of collagen-I, the main constituent of the ECM, increases the post-translational phosphorylation of Annexin A2 and subsequently causes the translocation of Annexin A2 to the extracellular surface. In the presence of collagen-I, we identified fibronectin as a novel interactor of Annexin A2, using mass spectrometry analysis. We then demonstrated that reducing Annexin A2 expression decreases the degradation of fibronectin by cancer cells and this effect on fibronectin turnover is increased according to collagen-I abundance. Discussion: Our results suggest that Annexin A2's role in promoting cancer progression is mediated by collagen-I and Annexin A2 maybe a therapeutic target in the bi-directional cross-talk between cancer cells and ECM remodeling that supports metastatic cancer progression.

Original languageEnglish
Article number1270436
Pages (from-to)1270436
JournalFrontiers in Oncology
Volume13
DOIs
Publication statusPublished - 2023

Keywords

  • Annexin A2
  • breast cancer
  • collagen-I
  • extracellular matrix
  • metastasis
  • tumor microenvironment

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