Oncogenic K-Ras Turns Death Receptors Into Metastasis-Promoting Receptors in Human and Mouse Colorectal Cancer Cells

Oncogenic Ras and B-Raf Proteins Positively Regulate Death Receptor 5 Expression through Co-activation of ERK and JNK Signaling

“…Fas) or other proteins in the death receptor pathways (e.g. caspase-8 and Fas-associated death domain) promotes tumor formation, growth, invasion, and even metastasis (45)(46)(47)(48)(49)(50)(51)(52). Thus, it is also possible that Ras-induced DR5 expression is involved in promoting Ras-mediated oncogenesis and/or metastasis, particularly under apoptosis-compromised conditions.…”

Dice

“…18 The expression of CD95 on cancer cells suggests that cancer cells maintain CD95 expression for activities other than apoptosis induction. Consistent with this assumption are data demonstrating roles for CD95 in promoting cancer cell migration, growth, epithelial-to-mesenchymal transition (EMT), and development, as shown in lung cancer, 19,20 colon cancer, [21][22][23][24] gastrointestinal cancers, 25,26 pancreatic cancer, 27,28 glioblastoma multiforme (GBM), 29 and in 22 cell lines representing various cancers. 30 Our most recent finding is that cancer fails to develop in mouse models of low-grade or endometrioid ovarian cancer or liver cancer unless CD95 is expressed, 14,31 suggesting that the reason cancer cells usually express CD95 goes beyond a function of CD95 as a tumor promoter.…”

How CD95 stimulates invasion

“…22 Indeed, CD95-induced formation of cell protrusions, tumor cell invasion and metastasis formation are cofilin-dependent phenomena. 12,22 Taken together, we propose that activation of the cofilin pathway following CD95 stimulation generates actin barbed ends that serve as nucleation sites for Rac-stimulated cortical actin remodeling (Fig. 2).…”

“…By contrast, CD95-induced migration and invasion does not appear to require an intact DD. 9,12,19,20 Nevertheless, in some tumor cell lines, invasion signaling by CD95 depends on caspase 8 11 and, by inference, on the DD to which it is recruited.…”

“…20 Likewise, CD95-induced tumor cell invasion and neutrophil migration also occur independently of the DD. 9,12 This strongly suggests that the invasion-and apoptosis-promoting signaling pathways already diverge at the level of the receptor.…”