Abstract
Microtentacles are mostly microtubule-based cell protrusions that are formed by detached tumor cells. Here, we report that the formation of tumor cell microtentacles depends on the presence and dynamics of guanine nucleotide-binding proteins of the septin family, which are part of the cytoskeleton. In matrix-attached breast, lung, prostate and pancreas cancer cells, septins are associated with the cytosolic actin cytoskeleton. Detachment of cells causes redistribution of septins to the membrane, where microtentacle formation occurs. Forchlorfenuron, which inhibits septin functions, blocks microtentacle formation. The small GTPase Cdc42 and its effector proteins Borgs regulate septins and are essential for microtentacle formation. Dominant active and inactive Cdc42 inhibit microtentacle formation indicating that the free cycling of Cdc42 between its active and inactive state is essential for septin regulation and microtentacle formation. Cell attachment and aggregation models suggest that septins play an essential role in the metastatic behavior of tumor cells.
Highlights
Metastasis is the leading cause of death among cancer patients [1,2,3]
We were tempted to study the role of septins in microtentacle formation in tumor cells
We observed that different types of tumor cells possess different profiles of septin proteins
Summary
Metastasis is the leading cause of death among cancer patients [1,2,3]. elucidation of the molecular mechanisms underlying cancer cell dissemination and metastasis is a main topic in cancer research. Factors and conditions that decrease actin polymerization like cytochalasin [4] or activation of cofilin [7] increase microtentacle formation, while compounds that inhibit microtubule formation, like colchicine [4], inhibit formation of microtentacles. These microtentacles appear to promote cell aggregation and increase the reattachment efficiency of tumor cells, thereby enhancing metastasis [4, 8, 9]
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