ARHGAP21 is a RhoGAP for RhoA and RhoC with a role in proliferation and migration of prostate adenocarcinoma cells

TY - JOUR

T1 - ARHGAP21 is a RhoGAP for RhoA and RhoC with a role in proliferation and migration of prostate adenocarcinoma cells

AU - Lazarini, Mariana

AU - Traina, Fabiola

AU - Machado-Neto, Joao A.

AU - Barcellos, Karin S. A.

AU - Moreira, Yuri B.

AU - Brandao, Marcelo M.

AU - Verjovski-Almeida, Sergio

AU - Ridley, Anne J.

AU - Olalla Saad, Sara T.

PY - 2013/2

Y1 - 2013/2

N2 - Background: Several Rho GTPase-activating proteins (RhoGAPs) are implicated in tumor progression through their effects on Rho GTPase activity. ARHGAP21 is a RhoGAP with increased expression in head and neck squamous cell carcinoma and with a possible role in glioblastoma tumor progression, yet little is known about the function of ARHGAP21 in cancer cells. Here we studied the role of ARHGAP21 in two prostate adenocarcinoma cell lines, LNCaP and PO, which respectively represent initial and advanced stages of prostate carcinogenesis. Results: ARHGAP21 is located in the nucleus and cytoplasm of both cell lines and its depletion resulted in decreased proliferation and increased migration of PO cells but not LNCaP cells. In PO cells, ARHGAP21 presented GAP activity for RhoA and RhoC and induced changes in cell morphology. Moreover, its silencing altered the expression of genes involved in cell proliferation and cytoskeleton organization, as well as the endothelin-1 canonical pathway. Conclusions: Our results reveal new functions and signaling pathways regulated by ARHGAP21, and indicate that it could contribute to prostate cancer progression.

AB - Background: Several Rho GTPase-activating proteins (RhoGAPs) are implicated in tumor progression through their effects on Rho GTPase activity. ARHGAP21 is a RhoGAP with increased expression in head and neck squamous cell carcinoma and with a possible role in glioblastoma tumor progression, yet little is known about the function of ARHGAP21 in cancer cells. Here we studied the role of ARHGAP21 in two prostate adenocarcinoma cell lines, LNCaP and PO, which respectively represent initial and advanced stages of prostate carcinogenesis. Results: ARHGAP21 is located in the nucleus and cytoplasm of both cell lines and its depletion resulted in decreased proliferation and increased migration of PO cells but not LNCaP cells. In PO cells, ARHGAP21 presented GAP activity for RhoA and RhoC and induced changes in cell morphology. Moreover, its silencing altered the expression of genes involved in cell proliferation and cytoskeleton organization, as well as the endothelin-1 canonical pathway. Conclusions: Our results reveal new functions and signaling pathways regulated by ARHGAP21, and indicate that it could contribute to prostate cancer progression.

KW - ARHGAP21

KW - RhoA

KW - RhoC

KW - Prostate adenocarcinoma

KW - PC3

KW - Endothelin-1

KW - GTPASE-ACTIVATING PROTEIN

KW - HEPATOCELLULAR-CARCINOMA CELLS

KW - ADHERENS JUNCTIONS

KW - ENDOTHELIN AXIS

KW - ARP2/3 COMPLEX

KW - ACTIN DYNAMICS

KW - PHASE-II

KW - CANCER

KW - INVASION

KW - METASTASIS

U2 - 10.1016/j.bbadis.2012.11.010

DO - 10.1016/j.bbadis.2012.11.010

M3 - Article

SN - 0925-4439

VL - 1832

SP - 365

EP - 374

JO - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

IS - 2

M1 - N/A

ER -