Abstract B3: HSP27 is required for invasion and metastasis triggered by hepatocyte growth factor

The Hepatocyte Growth Factor (HGF) also known as Scatter Factor, activates cancer cell invasion and metastasis. We show that in ovarian cancer cells HGF induced the phosphorylation of the small heat shock protein of 27KDa (HSP27) by activating the p38MAPK. HSP27 is increased in many cancers at advanced stage including ovarian cancer and associated with cancer resistance to therapy and poor patients' survival. The phosphorylation of HSP27 regulates both its chaperone activity and its control of cytoskeletal stability. We show that HSP27 was necessary for the motility in vitro and the remodeling of actin filaments induced by HGF. In vivo, HSP27 silencing impaired the ability of the highly metastatic, HGF-secreting ovarian cancer cells to give rise to spontaneous metastases. This was due to defective motility across the vessel wall and reduced growth. Indeed, HSP27 silencing impaired both the ability of ovarian cancer cells to form experimental haematogenous metastases and to grow as subcutaneous xenografts. Moreover, HSP27 suppression resulted in the sensitization of xenografts to low doses of the chemotherapeutic Paclitaxel, likely because HSP27 protected microtubules from bundling caused by the drug. Altogether, these data show that the HSP27 is required for the pro-invasive and pro-metastatic activity of HGF and suggest that HSP27 might be not only a marker of progression of ovarian cancer, but also a suitable target for therapy. Grant sponsors: This work has been supported by grants to M.F.D.: 2012 IG grant and 2010 Special Program Molecular Clinical Oncology 5xMille of the Italian Association of Cancer Research (AIRC), Project n° 9970, and Grant of the CARIPLO Foundation. Citation Format: Simona Pavan, Daniele Musiani, Erica Torchiaro, Giorgia Migliardi, Jessica Erriquez, Martina Olivero, Maria Flavia Di Renzo. HSP27 is required for invasion and metastasis triggered by hepatocyte growth factor. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B3.