reduced expression of the rock inhibitor rnd3 is associated with increased invasiveness and metastatic potential in mesenchymal tumor cells减少表达岩石抑制剂rnd3与增加的侵袭性和转移性间质肿瘤细胞的潜能.pdfVIP

Reduced Expression of the ROCK Inhibitor Rnd3 Is Associated with Increased Invasiveness and Metastatic Potential in Mesenchymal Tumor Cells 1 2 3 1 4 Cristina Belgiovine , Roberta Frapolli , Katiuscia Bonezzi , Ilaria Chiodi , Francesco Favero , Maurizia 4 5 6 3 2 Mello-Grand , Angelo P. Dei Tos , Elena Giulotto , Giulia Taraboletti , Maurizio D’Incalci , Chiara Mondello1* 1 Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy, 2 Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 3 Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy, 4 Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia, Biella, Italy, 5 Ospedale Generale di Treviso, Treviso, Italy, ` 6 Dipartimento di Genetica e Microbiologia, Universita di Pavia, Pavia, Italy Abstract Background: Mesenchymal and amoeboid movements are two important mechanisms adopted by cancer cells to invade the surrounding environment. Mesenchymal movement depends on extracellular matrix protease activity, amoeboid movement on the RhoA-dependent kinase ROCK. Cancer cells can switch from one mechanism to the other in response to different stimuli, limiting the efficacy of antimetastatic therapies. Methodology and Principal Findings: We investigated the acquisition and molecular regulation of the invasion capacity of neoplastically transformed human fibroblasts, which were able to induce sarcomas and metastases when injected into immunocompromised mice. We found that neoplastic transformation was associated with a change