The Role of WAVE2 Signaling in Cancer

Abstract

The Wiskott–Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE)—WAVE1, WAVE2 and WAVE3 regulate rapid reorganization of cortical actin filaments and have been shown to form a key link between small GTPases and the actin cytoskeleton. Upon receiving upstream signals from Rho-family GTPases, the WASP and WAVE family proteins play a significant role in polymerization of actin cytoskeleton through activation of actin-related protein 2/3 complex (Arp2/3). The Arp2/3 complex, once activated, forms actin-based membrane protrusions essential for cell migration and cancer cell invasion. Thus, by activation of Arp2/3 complex, the WAVE and WASP family proteins, as part of the WAVE regulatory complex (WRC), have been shown to play a critical role in cancer cell invasion and metastasis, drawing significant research interest over recent years. Several studies have highlighted the potential for targeting the genes encoding either part of or a complete protein from the WASP/WAVE family as therapeutic strategies for preventing the invasion and metastasis of cancer cells. WAVE2 is well documented to be associated with the pathogenesis of several human cancers, including lung, liver, pancreatic, prostate, colorectal and breast cancer, as well as other hematologic malignancies. This review focuses mainly on the role of WAVE2 in the development, invasion and metastasis of different types of cancer. This review also summarizes the molecular mechanisms that regulate the activity of WAVE2, as well as those oncogenic pathways that are regulated by WAVE2 to promote the cancer phenotype. Finally, we discuss potential therapeutic strategies that target WAVE2 or the WAVE regulatory complex, aimed at preventing or inhibiting cancer invasion and metastasis.

PPP2R1A Regulates Migration Persistence through the WAVE Shell Complex

“…The mechanism involves the exposure of the WCA domain of WAVE that binds and activates Arp2/3 8,9 . The RAC1-WAVE-Arp2/3 pathway is critical for development and normal adult life but is also involved in cancer [10][11][12] . Genes encoding subunits of the WAVE and Arp2/3 complexes are overexpressed in a variety of cancers, and this overexpression is associated with high tumor grade and poor patient prognosis 13 .…”

Role and mechanism of actin-related protein 2/3 complex signaling in cancer invasion and metastasis: A review

“…Colorectal cancer has become the third leading cause of cancer-related deaths in humans, accounting for 8.7% of all cancer deaths. [ 1 ] By immunohistochemistry, Otsubo et al [ 53 ] discovered significant overexpression of Arp2 and Arp3 proteins in cancer cells and stromal cells in 175 colorectal cancer specimens, whereas Arp2 and Arp3 were not expressed in normal colorectal mucosal epithelial or stromal cells. They proposed that stromal cells expressing Arp2 and Arp3 create a microenvironment that promotes cancer cell invasion prior to invasion.…”

“…Cancer cell invasion and migration are key components of cancer metastasis, which refer to the ability of cancer cells to move and cross the basement membrane and extracellular matrix, eventually moving and infiltrating into the surrounding tissue. [ 1 ] Cancer invasion and metastasis are complex processes that involve multiple cellular interactions and signaling pathways. However, cancer cells must undergo changes in actin cytoskeleton regulation and produce protrusion structures on their membranes, such as lamellipodia, invadopodia, and filopodia, in order to acquire a migratory phenotype.…”

The role of Raptor in lymphocytes differentiation and function

“…According to some research, WAVE2 is expressed more in hematopoietic cells and the deficiency of WAVE2 causes abnormal activation of T cells. It has also been reported that WAVE2-related signaling pathways play crucial roles in the invasion process and metastasis keeping of cancer cells and may be a novel target for cancer therapy in future ( 76 – 78 ). Scientists have found that WAVE 2 KO mice have severe autoimmune disease and inflammatory response compared to the WT controls ( 79 , 80 ).…”