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2014 ; 24
(11
): 1299-310
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Competition between human cells by entosis
#MMPMID25342560
Sun Q
; Luo T
; Ren Y
; Florey O
; Shirasawa S
; Sasazuki T
; Robinson DN
; Overholtzer M
Cell Res
2014[Nov]; 24
(11
): 1299-310
PMID25342560
show ga
Human carcinomas are comprised of complex mixtures of tumor cells that are known
to compete indirectly for nutrients and growth factors. Whether tumor cells could
also compete directly, for example by elimination of rivals, is not known. Here
we show that human cells can directly compete by a mechanism of engulfment called
entosis. By entosis, cells are engulfed, or cannibalized while alive, and
subsequently undergo cell death. We find that the identity of engulfing
("winner") and engulfed ("loser") cells is dictated by mechanical deformability
controlled by RhoA and actomyosin, where tumor cells with high deformability
preferentially engulf and outcompete neighboring cells with low deformability in
heterogeneous populations. We further find that activated Kras and Rac signaling
impart winner status to cells by downregulating contractile myosin, allowing for
the internalization of neighboring cells that eventually undergo cell death.
Finally, we compute the energy landscape of cell-in-cell formation, demonstrating
that a mechanical differential between winner and loser cells is required for
entosis to proceed. These data define a mechanism of competition in mammalian
cells that occurs in human tumors.
|*Entosis
[MESH]
|Actomyosin/metabolism
[MESH]
|Amides/pharmacology/therapeutic use
[MESH]
|Animals
[MESH]
|Apoptosis/drug effects
[MESH]
|Cell Line, Tumor
[MESH]
|Down-Regulation
[MESH]
|Enzyme Inhibitors/pharmacology/therapeutic use
[MESH]
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