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Abstract
BackgroundThe WASP (Wiskott-Aldrich syndrome protein) and WAVE (WASP Verpolin homologous) family of proteins are structurally related and responsible for regulation of actin polymerization through their interaction with actin related proteins 2&3 (ARP 2/3). WAVE-3 has exhibited an association with disease progression and poorer prognosis of certain malignancies. In the current study, we determined the role of WAVE-3 in hepatocyte growth factor induced cellular changes including cell matrix interaction, invasion and cellular motility, and pathways that may be responsible for the changes in prostate cancer cells.MethodsWe used hammer head ribozymes to knock down the expression of WAVE-3 in PC-3 prostate cancer cell line. In vitro cellular functional assays including growth, invasion, adhesion, motility and invasion, were performed to assess the effects of WAVE-3 knock down. Further experimentation was performed to investigate the role of different pathway through expression and phosphorylation status of various intermediate proteins.ResultsWAVE-3 knockdown reduced invasive potential and motility of prostate cancer cells. Following addition of HGF, control cells showed significantly increased invasion and motility (p value <0.5) and marked increase in cellular growth. However, WAVE-3 knockdown cell line failed to show any increase in these trends (p value <0.5) except increased growth compared with control cells. Further experiments revealed that HGF-induced activation of Paxillin was weakened by the knockdown of WAVE-3. Our study also indicated that reduced invasiveness following WAVE-3 knockdown, may be related to reduce activity of MMP-2.ConclusionsOur studies suggest a vital role of WAVE-3 in HGF induced invasion and migration in which Paxillin and MMP-2 are involved. Further study will shed light on its potential as therapeutic target to suppress local invasion and metastasis of prostate cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-015-0203-3) contains supplementary material, which is available to authorized users.
Highlights
The WASP (Wiskott-Aldrich syndrome protein) and WAVE (WASP Verpolin homologous) family of proteins are structurally related and responsible for regulation of actin polymerization through their interaction with actin related proteins 2&3 (ARP 2/3)
This study examined the effect of WAVE-3 on the Hepatocyte growth factor (HGF) induced migration and invasion of prostate cancer cells
Knockdown of WAVE-3 in PC-3 cells and the effect on cell growth Cells transfected with the anti-WAVE-3 ribozyme-2 transgene (PC-3 ΔWAVE-3 Rib2) exhibited a markedly reduced level of WAVE-3 expression compared controls and cells transfected with the anti-WAVE-3 ribozyme-1 transgene (PC-3 ΔWAVE-3Rib1) (Fig. 1)
Summary
The WASP (Wiskott-Aldrich syndrome protein) and WAVE (WASP Verpolin homologous) family of proteins are structurally related and responsible for regulation of actin polymerization through their interaction with actin related proteins 2&3 (ARP 2/3). We determined the role of WAVE-3 in hepatocyte growth factor induced cellular changes including cell matrix interaction, invasion and cellular motility, and pathways that may be responsible for the changes in prostate cancer cells. Cellular motility and cytoskeleton changes are integral parts of this process and depend upon actin polymerization. Cells exhibit these changes in response to interaction with the external environment through surface proteins. Through tightly regulated interactions with multiple structural and signaling molecules, serves as a nexus for the control of the Rho family of GTPases which act as essential regulators of the actin polymerization [4, 5]. It has been observed that an increase in Moazzam et al Cancer Cell International (2015) 15:51
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