Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs

López‐Garza, Ana; James, David; Creagh, Emma; Murray, James

doi:10.1002/1878-0261.70092

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Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs

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

Molecular Oncology

Swansea University Author: James Murray

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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
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa69814

first_indexed	2025-06-26T09:25:53Z
last_indexed	2025-10-17T09:24:15Z
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spelling	2025-10-16T14:32:52.8645889 v2 69814 2025-06-26 Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs 12d0a585fcfe66f83c4c21c6bca3197b 0000-0002-6928-2347 James Murray James Murray true false 2025-06-26 MEDS 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. Journal Article Molecular Oncology 0 Wiley 1574-7891 1878-0261 autophagy; chemoresistance; ovarian cancer; PTP4A3 14 7 2025 2025-07-14 10.1002/1878-0261.70092 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) Irish Research Council (Grant Number: GOIPG/2018/2724) 2025-10-16T14:32:52.8645889 2025-06-26T10:21:58.6423695 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Ana López‐Garza 1 David James 2 Emma Creagh 3 James Murray 0000-0002-6928-2347 4 69814__34796__75a18018d58c44f0997629ae86612589.pdf 69814.VoR.pdf 2025-07-17T16:12:44.1775827 Output 2796450 application/pdf Version of Record true Copyright: 2025 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License. true eng http://creativecommons.org/licenses/by/4.0/
title	Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs
spellingShingle	Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs James Murray
title_short	Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs
title_full	Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs
title_fullStr	Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs
title_full_unstemmed	Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs
title_sort	Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs
author_id_str_mv	12d0a585fcfe66f83c4c21c6bca3197b
author_id_fullname_str_mv	12d0a585fcfe66f83c4c21c6bca3197b_***_James Murray
author	James Murray
author2	Ana López‐Garza David James Emma Creagh James Murray
format	Journal article
container_title	Molecular Oncology
container_volume	0
publishDate	2025
institution	Swansea University
issn	1574-7891 1878-0261
doi_str_mv	10.1002/1878-0261.70092
publisher	Wiley
college_str	Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str	1
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description	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.
published_date	2025-07-14T05:24:27Z
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Targeting of PTP4A3 overexpression sensitises HGSOC cells towards chemotherapeutic drugs

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