Protein tyrosine phosphatase SHP2 promotes invadopodia formation through suppression of Rho signaling

// Wan-Chen Tsai 1 , Chien-Lin Chen 1, 3, 4 , Hong-Chen Chen 1, 2, 3, 4 1 Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan 2 Institutue of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan 3 Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan 4 Rong-Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan Correspondence to: Hong-Chen Chen, e-mail: hcchen@nchu.edu.tw Keywords: invadopodia, SHP2, phosphatase, invasion Received: February 21, 2015      Accepted: June 09, 2015      Published: June 19, 2015 ABSTRACT Invadopodia are actin-enriched membrane protrusions that are important for extracellular matrix degradation and invasive cell motility. Src homolog domain-containing phosphatase 2 (SHP2), a non-receptor protein tyrosine phosphatase, has been shown to play an important role in promoting cancer metastasis, but the underlying mechanism is unclear. In this study, we found that depletion of SHP2 by short-hairpin RNA suppressed invadopodia formation in several cancer cell lines, particularly in the SAS head and neck squamous cell line. In contrast, overexpression of SHP2 promoted invadopodia formation in the CAL27 head and neck squamous cell line, which expresses low levels of endogenous SHP2. The depletion of SHP2 in SAS cells significantly decreased their invasive motility. The suppression of invadopodia formation by SHP2 depletion was restored by the Clostridium botulinum C3 exoenzyme (a Rho GTPase inhibitor) or Y27632 (a specific inhibitor for Rho-associated kinase). Together, our results suggest that SHP2 may promote invadopodia formation through inhibition of Rho signaling in cancer cells.