The mechanisms of invasion and metastasis are poorly understood. Our previous studies demonstrated that cancer cell invasion may result from reorganization of membrane molecules, thereby initiating signaling pathways. To increase our understanding on how cancer cells govern metastases we studied the established LNCaP prostate cancer progression model. Herein we show that the bone metastatic derivative cell line, C4-2B, displays changes in adhesion to collagen type I and invasion into collagen type I. Moreover, we found that these changes were concomitant with activation of the FAK/src/paxillin/Rac/JNK signaling pathway and increased activity of matrix metalloproteinases (MMPs)-2 and -9. Inhibition of src and JNK resulted in inhibition of adhesion and invasion, and deactivation of the signaling molecules in the identified pathway as well as reduced activity of MMPs. Additionally, we found a pivotal role for the integrin α2 subunit since lateral redistribution and clustering were responsible for activation of the downstream signaling and function blocking of the integrin α2 subunit resulted in poor adhesion and inhibition of invasion. In conclusion, our results suggest that invasion of prostate cancer cells can be ascribed to reorganization and clustering of integrin α2 subunits, resulting in activation of associated FAK/src/paxillin/Rac/JNK, leading to increased activity of MMPs and thus invasion.

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