Ceppi Paolo, Hadji Abbas, Kohlhapp Frederick J, Pattanayak Abhinandan, Hau Annika, Liu Xia, Liu Huiping, Murmann Andrea E, Peter Marcus E
Division Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Department of Pathology and Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Nat Commun. 2014 Nov 4;5:5238. doi: 10.1038/ncomms6238.
CD95 (APO-1/Fas) is a death receptor used by immune cells to kill cancer cells through induction of apoptosis. However, the elimination of CD95 or its ligand, CD95L, from cancer cells results in death induced by CD95R/L elimination (DICE), a type of cell death that resembles a necrotic form of mitotic catastrophe suggesting that CD95 protects cancer cells from cell death. We now report that stimulation of CD95 on cancer cells or reducing miR-200c levels increases the number of cancer stem cells (CSCs), which are more sensitive to induction of DICE than non-CSC, while becoming less sensitive to CD95-mediated apoptosis. In contrast, induction of DICE or overexpression of miR-200c reduces the number of CSCs. We demonstrate that CSCs and non-CSCs have differential sensitivities to CD95-mediated apoptosis and DICE, and that killing of cancer cells can be maximized by concomitant induction of both cell death mechanisms.
CD95（APO-1/Fas）是一种死亡受体，免疫细胞可通过诱导细胞凋亡利用它来杀死癌细胞。然而，从癌细胞中去除CD95或其配体CD95L会导致由CD95R/L去除诱导的死亡（DICE），这是一种类似于有丝分裂灾难坏死形式的细胞死亡，表明CD95可保护癌细胞免于细胞死亡。我们现在报告，刺激癌细胞上的CD95或降低miR-200c水平会增加癌症干细胞（CSC）的数量，与非CSC相比，CSC对DICE诱导更敏感，而对CD95介导的细胞凋亡敏感性降低。相反，诱导DICE或过表达miR-200c会减少CSC的数量。我们证明，CSC和非CSC对CD95介导的细胞凋亡和DICE具有不同的敏感性，并且通过同时诱导两种细胞死亡机制可以最大程度地杀死癌细胞。
