Open AccessCXCL13 mediates prostate cancer cell proliferation through JNK signalling and invasion through ERK activation
Author(s) -
ElHaibi C. P.,
Singh R.,
Sharma P. K.,
Singh S.,
Lillard J. W.
Publication year - 2011
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2011.00757.x
Subject(s) - lncap , cell growth , protein kinase b , cancer research , microbiology and biotechnology , mapk/erk pathway , signal transduction , biology , cancer cell , chemistry , cancer , biochemistry , genetics
Objectives: The focus of this study was to determine the dedicator of cytokinesis 2 (DOCK2), extracellular signal‐regulated kinase 1/2 (ERK1/2), c‐Jun N‐terminal kinase‐1 (JNK) and Akt signals involved in CXCL13‐mediated prostate cancer (PCa) cell invasion and proliferation. Materials and methods: Androgen‐sensitive (LNCaP), hormone‐refractory (PC3) cells and normal cells (RWPE‐1) were used to determine CXCL13‐mediated PCa cell invasion and proliferation. Immuno‐blotting, fast activated cell‐based (FACE) ELISA, caspase activity, cell invasion and proliferation assays were performed to ascertain some of the signalling events involved in PCa cell proliferation and invasion. Results: Unlike androgen‐sensitive LNCaP cells, we report for the first time that the hormone‐refractory cell line, PC3, expresses DOCK2. CXCL13‐mediated LNCaP and PC3 cell invasion was regulated by Akt and ERK1/2 activation in a DOCK2‐independent fashion. CXCL13 also promoted LNCaP cell proliferation in a JNK‐dependent fashion even in the absence of DOCK2. In contrast, CXCL13 induced PC3 cell proliferation through JNK activation, which required DOCK2. Conclusions: Our results show CXCL13‐mediated PCa cell invasion requires Akt and ERK1/2 activation and suggests a new role for DOCK2 in proliferation of hormone‐refractory CXCR5‐positive PCa cells.