The role of PKC in CXCL8 and CXCL10 directed prostate, breast and leukemic cancer cell migration

Al Assaf, Enana and Mueller, Anja (2020) The role of PKC in CXCL8 and CXCL10 directed prostate, breast and leukemic cancer cell migration. European Journal of Pharmacology, 886. ISSN 0014-2999

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Abstract

Migration of tumour cells is a fundamental process for the formation and progression of metastasis in malignant diseases. Chemokines binding to their cognate receptors induce the migration of cancer cells, however, the molecular signalling pathways involved in this process are not fully understood. Protein kinase C (PKC) has been shown to regulate cell migration, adhesion and proliferation. In order to identify a connection between PKC and tumour progression in breast, prostate and leukaemia cells, the effect of PKC on CXCL8 or CXCL10-mediated cell migration and morphology was analysed. We tested the speed of the migrating cells, morphology, and chemotaxis incubated with different PKC isoforms inhibitors- GF109203X, staurosporine and PKCζ pseudosubstrate inhibitor (PKCζi). We found that the migration of CXCL8-driven PC3 and MDA-MB231 cells in the presence of conventional, novel or atypical PKCs was not affected, but atypical PKCζ is crucial for THP-1 chemotaxis. The speed of CXCL10-activated PC3 and MDA-MB231 cells was significantly reduced in the presence of conventional, novel and atypical PKCζ. THP-1 chemotaxis was again affected by atypical PKCζi. On the other hand, cell area, circularity or aspect ratio were affected by staurosporine in CXCL8 or CXCL10-activated cells, demonstrating a role of PKCα in the rearrangement of the cytoskeleton regardless of the effect on the migration. Consequently, this allows the speculation that different PKC isoforms induce different outcomes in migration and actin cytoskeleton based on the chemokine receptor and/or the cell type.

Item Type: Article
Uncontrolled Keywords: cxcr1,cxcr2,cxcr3,chemokine receptors,migration,morphology,protein kinase c,pharmacology ,/dk/atira/pure/subjectarea/asjc/3000/3004
Faculty \ School: Faculty of Science > School of Pharmacy
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 31 Jul 2020 23:50
Last Modified: 18 Aug 2020 23:55
URI: https://ueaeprints.uea.ac.uk/id/eprint/76310
DOI: 10.1016/j.ejphar.2020.173453

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