Apoptotic stress-induced FGF signalling promotes non-cell autonomous resistance to cell death.
Apoptotic stress-induced FGF signalling promotes non-cell autonomous resistance to cell death.
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DOI：
10.1038/s41467-021-26613-0
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发表时间：
2021-11-12
影响因子：
16.6
通讯作者：
Tait SWG
中科院分区：
文献类型：
--
作者：
Bock FJ;Sedov E;Koren E;Koessinger AL;Cloix C;Zerbst D;Athineos D;Anand J;Campbell KJ;Blyth K;Fuchs Y;Tait SWG
受损或多余的细胞通常通过凋亡消除。虽然凋亡是一个细胞自主的过程，但凋亡细胞以不同的方式与其环境沟通。在这里，我们描述了一种机制，使细胞凋亡的压力下，可以促进相邻细胞的生存。我们发现，在凋亡应激时，细胞释放生长因子FGF 2，导致MEK-ERK依赖性转录上调促生存BCL-2蛋白在非细胞自主的方式。这种促存活BCL-2蛋白的瞬时上调保护邻近细胞免于凋亡。因此，我们在某些癌症类型中发现FGF信号传导、BCL-2表达与预后不良之间的相关性。在体内，MCL-1的上调在皮肤修复期间以FGF依赖性方式发生，其调节愈合动力学。重要的是，与FGF-受体抑制剂共治疗或去除凋亡应激恢复了对细胞毒性治疗的凋亡敏感性并延迟伤口愈合。这些数据揭示了凋亡应激下的细胞可以增加对周围细胞中细胞死亡的抵抗的途径。除了介导细胞毒性药物耐药性外，该过程还提供了组织损伤和修复之间的潜在联系。细胞凋亡是一个细胞过程，消除受损或多余的细胞。在这里，作者表明，经历凋亡应激的细胞分泌生长因子FGF 2，其上调邻近细胞中的促生存BCL-2蛋白，从而促进其存活。
Damaged or superfluous cells are typically eliminated by apoptosis. Although apoptosis is a cell-autonomous process, apoptotic cells communicate with their environment in different ways. Here we describe a mechanism whereby cells under apoptotic stress can promote survival of neighbouring cells. We find that upon apoptotic stress, cells release the growth factor FGF2, leading to MEK-ERK-dependent transcriptional upregulation of pro-survival BCL-2 proteins in a non-cell autonomous manner. This transient upregulation of pro-survival BCL-2 proteins protects neighbouring cells from apoptosis. Accordingly, we find in certain cancer types a correlation between FGF-signalling, BCL-2 expression and worse prognosis. In vivo, upregulation of MCL-1 occurs in an FGF-dependent manner during skin repair, which regulates healing dynamics. Importantly, either co-treatment with FGF-receptor inhibitors or removal of apoptotic stress restores apoptotic sensitivity to cytotoxic therapy and delays wound healing. These data reveal a pathway by which cells under apoptotic stress can increase resistance to cell death in surrounding cells. Beyond mediating cytotoxic drug resistance, this process also provides a potential link between tissue damage and repair. Apoptosis is a cellular process that eliminates damaged or superfluous cells. Here the authors show that cells undergoing apoptotic stresss secrete the growth factor FGF2, which upregulates pro-survival BCL-2 proteins in neighbouring cells, thereby promoting their survival.
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影响因子：
--
作者：
Casara P;Davidson J;Claperon A;Le Toumelin-Braizat G;Vogler M;Bruno A;Chanrion M;Lysiak-Auvity G;Le Diguarher T;Starck JB;Chen I;Whitehead N;Graham C;Matassova N;Dokurno P;Pedder C;Wang Y;Qiu S;Girard AM;Schneider E;Gravé F;Studeny A;Guasconi G;Rocchetti F;Maïga S;Henlin JM;Colland F;Kraus-Berthier L;Le Gouill S;Dyer MJS;Hubbard R;Wood M;Amiot M;Cohen GM;Hickman JA;Morris E;Murray J;Geneste O
通讯作者：
Geneste O
影响因子：
64.8
作者：
De Simone A;Evanitsky MN;Hayden L;Cox BD;Wang J;Tornini VA;Ou J;Chao A;Poss KD;Di Talia S
通讯作者：
Di Talia S
影响因子：
11.4
作者：
Konig, A;Menzel, T;Gabrilove, JL
通讯作者：
Gabrilove, JL
影响因子：
21.3
作者：
Giampazolias E;Zunino B;Dhayade S;Bock F;Cloix C;Cao K;Roca A;Lopez J;Ichim G;Proïcs E;Rubio-Patiño C;Fort L;Yatim N;Woodham E;Orozco S;Taraborrelli L;Peltzer N;Lecis D;Machesky L;Walczak H;Albert ML;Milling S;Oberst A;Ricci JE;Ryan KM;Blyth K;Tait SWG
通讯作者：
Tait SWG
影响因子：
12.4
作者：
Bock, F. J.;Krumschnabel, G.;Villunger, A.
通讯作者：
Villunger, A.