Loss of proline-rich tyrosine kinase 2 function induces spreading and motility of epithelial prostate cells.
Although prostate carcinoma is an aggressive cancer preferentially metastasizing to the bones, many prostate tumors remain localized and confined to the prostate indefinitely. Prediction of the behavior of anatomically localized and moderately differentiated prostate tumors remains difficult because of lack of prognostic markers. Cell motility is an important step in the progression of epithelial tumor toward invasive metastatic carcinomas and changes in the expression and function of adhesion molecules contribute to the acquisition of a more malignant phenotype. Proline-rich tyrosine kinase 2 (Pyk2) is implicated in regulating the organization of actin cytoskeleton, a process critical for cell migration, mitosis, and tumor metastasis. In this report, we investigated whether Pyk2 played a role in the acquisition of an aggressive phenotype in prostate cell. Data reported here demonstrate that loss of Pyk2 kinase function results in induction of cell motility and migration in EPN cells, a line of non-transformed epithelial cells derived from human normal prostate tissue. Changes in motility and migration of prostate cells were associated with changes in the expression of several proteins involved in cell adhesion and reorganization of actin cytoskeleton. Ablation of Pyk2 kinase activity caused a dramatic decrease of the expression of E-cadherin and IRS1 and an increase of the expression of alpha5-integrin. In addition, a massive reorganization of actin cytoskeleton was observed. Our data indicate that Pyk2 plays a central role in the mechanism that regulate cell-cell and cell-substrate interaction and lack of its kinase activity induces prostate cells to acquire a malignant, migrating phenotype.
de Amicis
Francesca
F
Dipartimento Farmaco-Biologico, Università della Calabria Arcavacata, Cosenza, Italy.
Lanzino
Marilena
M
Kisslinger
Annamaria
A
Calì
Gaetano
G
Chieffi
Paolo
P
Andò
Sebastiano
S
Mancini
Francesco Paolo
FP
Tramontano
Donatella
D
D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004847:Epithelial Cells / Q000502:physiology; D051418:Focal Adhesion Kinase 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D022001:Focal Adhesions; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D039482:Integrin alpha5 / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000201:enzymology*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014162:Transfection
D015820:Cadherins; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D039482:Integrin alpha5; D010750:Phosphoproteins; D051418:Focal Adhesion Kinase 2