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Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs

Ana López‐Garza, David James, Emma Creagh, James Murray Orcid Logo

Molecular Oncology

Swansea University Author: James Murray Orcid Logo

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DOI (Published version): 10.1002/1878-0261.70092

Abstract

Ovarian cancer (OC) has the highest mortality rate of all gynaecological malignancies, partly attributable to its propensity for chemotherapy resistance. The most common subtype of OC is serous, of which high-grade serous ovarian cancer (HGSOC) is the most lethal subtype. Protein tyrosine phosphatas...

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Published in: Molecular Oncology
ISSN: 1574-7891 1878-0261
Published: Wiley 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa69814
Abstract: Ovarian cancer (OC) has the highest mortality rate of all gynaecological malignancies, partly attributable to its propensity for chemotherapy resistance. The most common subtype of OC is serous, of which high-grade serous ovarian cancer (HGSOC) is the most lethal subtype. Protein tyrosine phosphatase 4A3 (PTP4A3) overexpression is implicated in tumour cell invasion and metastasis by upregulating the PI3K/Akt/mTORC1 axis. Previously, we reported that PTP4A3 increased the survival of non-serous OC cells by activating the autophagy pathway. Here, we investigated the impact of PTP4A3 on cell proliferation, autophagy and chemoresistance in HGSOC cells and whether targeting PTP4A3 in HGSOC cells that overexpress this phosphatase would sensitise them to existing chemotherapeutic drugs. Gene silencing of PTP4A3 resulted in the upregulation of compensatory mechanisms that overcame the loss of PTP4A3 expression, but this was mitigated by pan-PTP4A inhibition with JMS-053 in HGSOC cells. Moreover, shRNA-mediated silencing of PTP4A3 sensitised HGSOC cells to clinically relevant chemotherapeutic drugs. Overall, we show that compensatory mechanisms from PTP4A1 and PTP4A2 can arise when specifically targeting PTP4A3 in HGSOC and that pan-PTP4A inhibition can overcome those effects.
Keywords: autophagy; chemoresistance; ovarian cancer; PTP4A3
College: Faculty of Medicine, Health and Life Sciences
Funders: Irish Research Council (Grant Number: GOIPG/2018/2724)

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