The role of PKC and PKD in CXCL12 and CXCL13 directed malignant melanoma and acute monocytic leukemic cancer cell migration

Hamshaw, Isabel ORCID: https://orcid.org/0000-0001-6445-0738, Ellahouny, Youssef, Malusickis, Artur, Newman, Lia, Ortiz-Jacobs, Dante and Mueller, Anja ORCID: https://orcid.org/0000-0003-0774-0434 (2024) The role of PKC and PKD in CXCL12 and CXCL13 directed malignant melanoma and acute monocytic leukemic cancer cell migration. Cellular Signalling, 113. ISSN 0898-6568

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Abstract

Cancer metastasis is the leading cause of cancer related mortality. Chemokine receptors and proteins in their downstream signalling axis represent desirable therapeutic targets for the prevention of metastasis. Despite this, current therapeutics have experienced limited success in clinical trials due to a lack of insight into the downstream signalling pathway of specific chemokine receptor cascades in different tumours. In this study, we investigated the role of protein kinase C (PKC) and protein kinase D (PKD) in CXCL12 and CXCL13 stimulated SK-MEL-28 (malignant melanoma) and THP-1 (acute monocytic leukaemia) cell migration. While PKC and PKD had no active role in CXCL12 or CXCL13 stimulated THP-1 cell migration, PKC and PKD inhibition reduced CXCL12 stimulated migration and caused profound effects upon the cytoskeleton of SK-MEL-28 cells. Furthermore, only PKC and not PKD inhibition reduced CXCL13 stimulated migration in SK-MEL-28 cells however PKC inhibition failed to stimulate any changes to the actin cytoskeleton. These findings indicate that PKC inhibitors would be a useful therapeutic for the prevention of both CXCL12 and CXCL13 stimulated migration and PKD inhibitors for CXCL12 stimulated migration in malignant melanoma.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Pharmacy
UEA Research Groups:	Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
Depositing User:	LivePure Connector
Date Deposited:	07 Nov 2023 02:49
Last Modified:	28 Nov 2023 02:59
URI:	https://ueaeprints.uea.ac.uk/id/eprint/93581
DOI:	10.1016/j.cellsig.2023.110966

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