Inactivation of the WASF3 gene in prostate cancer cells leads to suppression of tumorigenicity and metastases.
BACKGROUND
The WASF3 protein is involved in cell movement and invasion, and to investigate its role in prostate cancer progression we studied the phenotypic effects of knockdown in primary tumors and cell lines.


METHODS
ShRNA was used to knockdown WASF3 function in prostate cell lines. Cell motility (scratch wound assay), anchorage independent growth and in vivo tumorigenicity and metastasis were then compared between knockdown and wild-type cells.


RESULTS
Increased levels of expression were seen in high-grade human prostate cancer and in the PC3 and DU145 cell lines. Inactivation of WASF3 using shRNAs reduced cell motility and invasion in these cells and reduced anchorage independent growth in vitro. The loss of motility was accompanied by an associated increase in stress fiber formation and focal adhesions. When injected subcutaneously into severe combined immunodeficiency (SCID) mice, tumor formation was significantly reduced for PC3 and DU145 cells with WASF3 knockdown and in vivo metastasis assays using tail vain injection showed a significant reduction for PC3 and DU145 cells. The loss of the invasion phenotype was accompanied by down-regulation of matrix metalloproteinase 9.


CONCLUSIONS
Overall, these observations demonstrate a critical role for WASF3 in the progression of prostate cancer and identify a potential target to control tumorigenicity and metastasis.
Teng
Y
Y
MCG Cancer Center, School of Medicine, Medical College of Georgia, CN4112, 1120 15th Street, Augusta, GA 30912, USA.
Ren
M Q
MQ
Cheney
R
R
Sharma
S
S
Cowell
J K
JK
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics* / Q000378:metabolism
C120153:WASF3 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D020780:Matrix Metalloproteinase 9