title: Cell migration towards CXCL12 in leukemic cells compared to breast cancer cells.
abstract: Chemotaxis or directed cell migration is mediated by signalling events initiated by binding of chemokines to their cognate receptors and the activation of a complex signalling cascade. The molecular signalling pathways involved in cell migration are important to understand cancer cell metastasis. Therefore, we investigated the molecular mechanisms of CXCL12 induced cell migration and the importance of different signalling cascades that become activated by CXCR4 in leukemic cells versus breast cancer cells. We identified Src kinase as being essential for cell migration in both cancer types, with strong involvement of the Raf/MEK/ERK1/2 pathway. We did not detect any involvement of Ras or JAK2/STAT3 in CXCL12 induced migration in Jurkat cells. Preventing PKC activation with inhibitors does not affect migration in Jurkat cells at all, unlike in the adherent breast cancer cell line MCF-7 cells. However, in both cell lines, knock down of PKCα prevents migration towards CXCL12, whereas the expression of PKCζ is less crucial for migration. PI3K activation is essential in both cell types, however LY294002 usage in MCF-7 cells does not block migration significantly. These results highlight the importance of verifying specific signalling pathways in different cell settings and with different approaches.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Shirley C
authors.initials: SC
authors.lastname: Mills
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Poh Hui
authors.initials: PH
authors.lastname: Goh
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Jossie
authors.initials: J
authors.lastname: Kudatsih
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Sithembile
authors.initials: S
authors.lastname: Ncube
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Renu
authors.initials: R
authors.lastname: Gurung
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Will
authors.initials: W
authors.lastname: Maxwell
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK. Electronic address: anja.mueller@uea.ac.uk.
authors.forename: Anja
authors.initials: A
authors.lastname: Mueller
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D007938:Leukemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D061986:MCF-7 Cells; D009025:Morpholines / Q000494:pharmacology; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D002867:Chromones; D009025:Morpholines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C497255:PRKCE protein, human; D051744:Protein Kinase C-epsilon; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Chemokine receptor; Chemotaxis; Protein kinase; Src