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2017 ; 8
(44
): 76686-76698
Nephropedia Template TP
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Septin remodeling is essential for the formation of cell membrane protrusions
(microtentacles) in detached tumor cells
#MMPMID29100341
Østevold K
; Meléndez AV
; Lehmann F
; Schmidt G
; Aktories K
; Schwan C
Oncotarget
2017[Sep]; 8
(44
): 76686-76698
PMID29100341
show ga
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.