ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells.
Aberrant regulation in the adhesive ability of cancer cells is closely associated with their metastatic activity. In this study, we examine the role of ErbB-2 in regulating the adhesive ability of androgen receptor (AR)-positive human prostate cancer (PCa) cells, the major cell population of PCa. Utilizing different LNCaP and MDA PCa2b cells as model systems, we found that ErbB-2 activity was correlated with PYK2 activity and adhesive ability in those cells. Increased ErbB-2 expression or activity in LNCaP C-33 cells enhanced PYK2 activation and cell adhesion, while the high PYK2 activity and the rapid adhesion of LNCaP C-81 cells were decreased by diminishing ErbB-2 expression or activity. Knockdown studies revealed the predominant role of ErbB-2 in regulating LNCaP C-81 cell adhesion. Coimmunoprecipitation showed that C-81 cells had increased interaction between ErbB-2 and PYK2. Elevated ErbB-2 activity in LNCaP cells correlated with increased ERK/MAPK activity and enhanced adhesive ability, which were abolished by the expression of K457A-PYK2 mutant or the treatment of PD98059, a MEK inhibitor. In summary, our data suggested that ErbB-2, via PYK2-ERK/MAPK, upregulates the adhesive ability of AR-positive human PCa cells.
Yuan
T-C
TC
Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
Lin
F-F
FF
Veeramani
S
S
Chen
S-J
SJ
Earp
H S
HS
Lin
M-F
MF
D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009930:Organic Chemicals / Q000494:pharmacology; D011471:Prostatic Neoplasms; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D004791:Enzyme Inhibitors; D051418:Focal Adhesion Kinase 2; D009930:Organic Chemicals; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011994:Recombinant Proteins; C466090:PD 98058