Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma.
Stem cell senescence drives age-attenuated induction of pituitary tumours in mouse models of paediatric craniopharyngioma.
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DOI：
10.1038/s41467-017-01992-5
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发表时间：
2017-11-28
影响因子：
16.6
通讯作者：
Martinez-Barbera JP
中科院分区：
文献类型：
--
作者：
Gonzalez-Meljem JM;Haston S;Carreno G;Apps JR;Pozzi S;Stache C;Kaushal G;Virasami A;Panousopoulos L;Mousavy-Gharavy SN;Guerrero A;Rashid M;Jani N;Goding CR;Jacques TS;Adams DJ;Gil J;Andoniadou CL;Martinez-Barbera JP
衰老细胞可能通过激活衰老相关分泌表型（SASP）促进肿瘤进展，这些细胞是否能够在体内启动肿瘤发生尚不清楚。在Sox 2+年轻成人垂体干细胞中表达致癌β-连环蛋白导致形成干细胞簇，并诱导类似于人成釉细胞瘤性颅咽管瘤（ACP）的肿瘤，其以旁分泌方式来源于Sox 2 −细胞。在这里，我们揭示了这种旁分泌肿瘤发生的机制。我们表明Hesx 1+胚胎前体中致癌β-连环蛋白的表达也会导致干细胞簇和旁分泌肿瘤。我们发现，人类和小鼠集群是类似的，并共享一个共同的签名衰老和SASP。最后，我们表明，小鼠衰老和SASP反应减少表现出降低的肿瘤诱导潜力。总之，我们提供的证据表明，衰老和干细胞相关的SASP驱动细胞转化和肿瘤在体内以年龄依赖性的方式启动。衰老细胞可以通过激活衰老相关分泌表型（SASP）促进肿瘤进展。在这里，作者表明，SASP激活与非细胞自主细胞转化和成釉细胞瘤性颅咽管瘤的体内模型中的肿瘤起始有关。
Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2− cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis. We show that expression of oncogenic β-catenin in Hesx1+ embryonic precursors also results in stem cell clusters and paracrine tumours. We reveal that human and mouse clusters are analogous and share a common signature of senescence and SASP. Finally, we show that mice with reduced senescence and SASP responses exhibit decreased tumour-inducing potential. Together, we provide evidence that senescence and a stem cell-associated SASP drive cell transformation and tumour initiation in vivo in an age-dependent fashion. Senescent cells can promote tumour progression through the activation of a senescenceassociated secretory phenotype (SASP). Here, the authors show that SASP activation is associated with non-cell autonomous cell transformation and tumour initiation in an in vivo model of adamantinomatous craniopharyngioma.
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影响因子：
11.2
作者：
Bavik, C;Coleman, I;Nelson, PS
通讯作者：
Nelson, PS
影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
胶质瘤起始细胞通过PDGF信号传导在肿瘤组织重塑过程中促进宿主胶质细胞的恶性转化
影响因子：
9.7
作者：
Chen, Yanming;Wang, Zhongyong;Dong, Jun
通讯作者：
Dong, Jun
影响因子：
5.6
作者：
Hofmann, Bernd M.;Kreutzer, Juergen;Buslei, Rolf
通讯作者：
Buslei, Rolf
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM