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Co‑localisation of intra‑nuclear membrane type‑1 matrix metalloproteinase and hypoxia inducible factor‑2α in osteosarcoma and prostate carcinoma cells

Lookup NU author(s): Dr Corey ChanORCiD, Dr Emma Haagensen, Dr Hayeit Tensaout, Dr Kate Rennie, Dr Zakareya Gamie, Dr Mark Birch, Craig Gerrand, Professor Craig Robson, Professor John LunecORCiD, Dr Kenneth RankinORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2021 Spandidos Publications. All rights reserved.Increased membrane type‑1 matrix metalloproteinase (MT1‑MMP) expression in osteosarcoma is predictive of poor prognosis and directs bone metastasis in prostate carcinoma. MT1‑MMP subcellular localisation varies with oxygen tension, and, therefore, the aim of the present study was to assess protein interactions between MT1‑MMP and the hypoxia inducible factors (HIF‑1α and HIF‑2α). MT1‑MMP protein expression was investigated across a panel of cancer cell lines, including a positive and negative control. The hypoxia‑induced alteration in subcellular location of MT1‑MMP, HIF‑1α and HIF‑2α in the U2OS osteosarcoma cell line was assessed using subcellular fractionation. A proximity ligation assay was utilised to assess protein to protein interactions in the osteosarcoma U2OS and prostate carcinoma PC3 cell lines. U2OS and PC3 cells exhib‑ ited a significantly increased intra‑nuclear interaction between MT1‑MMP and HIF‑2α in response to hypoxia. The role of this warrants further investigation as it may unveil novel opportuni‑ ties to target MT1‑MMP, which is of particular significance for osteosarcoma since current treatment options are limited.

Publication metadata

Author(s): Chan CD, Haagensen EJ, Tensaout HA, Rennie KJ, Gamie Z, Barry J, Birch MA, Gerrand CH, Nisar S, Robson CN, Lunec J, Rankin KS

Publication type: Article

Publication status: Published

Journal: Oncology Letters

Year: 2021

Volume: 21

Issue: 2

Print publication date: 01/02/2021

Online publication date: 31/12/2020

Acceptance date: 04/08/2020

Date deposited: 30/03/2022

ISSN (print): 1792-1074

ISSN (electronic): 1792-1082

Publisher: Spandidos Publications


DOI: 10.3892/ol.2020.12419


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