Oxidative stress-responsive 1 kinase catalytic activity promotes triple negative breast cancer oncogenic potential

Fdel, Azeza M., Waters, Loren, Sharma, Ira, Jones, Samuel, Gee, Julia ORCID: https://orcid.org/0000-0001-6483-2015, Atack, John R. ORCID: https://orcid.org/0000-0002-3410-791X, Banerjee, Sourav and Mehellou, Youcef ORCID: https://orcid.org/0000-0001-5720-8513 2025. Oxidative stress-responsive 1 kinase catalytic activity promotes triple negative breast cancer oncogenic potential. ACS pharmacology & translational science 10.1021/acsptsci.4c00603

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Abstract

The protein kinase OSR1 has been highlighted as a biomarker for a poor prognosis in breast cancer (BC) patients. To further decipher the mechanism underpinning this, we studied the expression, phosphorylation status, and catalytic activity of OSR1 across a series of BC cell lines. OSR1 was found to be expressed across the various luminal and triple negative BC (TNBC) cell lines studied, although it was only constitutively active in the highly migratory TNBC cell line MDA-MB-231. Although this cell line carries p53 mutations, our data indicated that OSR1 constitutive kinase activity of the OSR1 in MDA-MB-231 was independent of p53. Interestingly, the inhibition of OSR1 had no significant impact on MDA-MB-231 cell viability, but it was found to contribute to its substantial cell migration and invasion, as this was significantly attenuated by the WNK/OSR1 inhibitor WNK463. Analogously, the overexpression of constitutively active OSR1 in the poorly migrating BC cell line MCF7 enhanced its cell mobility. Collectively, our results indicate that the pharmacological inhibition of OSR1 could be a promising novel strategy for preventing the oncogenic potential of TNBC.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Schools > Biosciences Schools > Pharmacy
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Start Date: 2025-02-27
Publisher:	American Chemical Society
ISSN:	2575-9108
Funders:	UKRI
Date of First Compliant Deposit:	11 March 2025
Date of Acceptance:	24 February 2025
Last Modified:	24 Mar 2025 18:18
URI:	https://orca.cardiff.ac.uk/id/eprint/176795

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