Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis.
Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis.
复制标题
DOI：
10.1016/j.cmet.2018.08.007
复制
发表时间：
2019-01-08
期刊：
影响因子：
29
通讯作者：
Lengyel E
中科院分区：
文献类型：
--
作者：
Curtis M;Kenny HA;Ashcroft B;Mukherjee A;Johnson A;Zhang Y;Helou Y;Batlle R;Liu X;Gutierrez N;Gao X;Yamada SD;Lastra R;Montag A;Ahsan N;Locasale JW;Salomon AR;Nebreda AR;Lengyel E
成功的转移需要基质细胞和癌细胞的共同进化。我们使用细胞培养中氨基酸的稳定同位素标记（SILAC）结合定量的无标记磷酸蛋白质组学来研究共培养后卵巢癌细胞和人源性癌症相关成纤维细胞（CAF）中的双向信号传导。在癌细胞中，与CAF的相互作用支持在常氧条件下的糖原分解，并诱导磷酸葡萄糖变位酶1（PGM1）的磷酸化和活化，PGM1是一种参与糖原代谢的酶。糖原被汇集到糖酵解中，导致与人CAF共培养的癌细胞的增殖、侵袭和转移增加。癌细胞的糖原动员依赖于CAFs中p38α MAPK的激活。在体内，CAF中p38α的缺失和癌细胞中糖原磷酸化酶的抑制减少了转移，表明糖原是癌细胞用于促进转移性肿瘤生长的能量来源。等人的研究表明，卵巢癌细胞可以动员糖原作为能量来源，导致其与癌症相关成纤维细胞（CAF）相互作用后增殖、侵袭和转移增加。这一过程依赖于CAFs中p38α MAPK的激活，抑制该途径可减少体内转移性肿瘤的生长。
Successful metastasis requires the co-evolution of stromal and cancer cells. We used stable isotope labeling of amino acids in cell culture (SILAC) coupled with quantitative, label-free phosphoproteomics to study the bidirectional signaling in ovarian cancer cells and human-derived, cancer-associated fibroblasts (CAFs) after co-culture. In cancer cells, the interaction with CAFs supported glycogenolysis under normoxic conditions and induced phosphorylation and activation of phosphoglucomutase 1 (PGM1), an enzyme involved in glycogen metabolism. Glycogen was funneled into glycolysis, leading to increased proliferation, invasion, and metastasis of cancer cells co-cultured with human CAFs. Glycogen mobilization in cancer cells was dependent on p38α MAPK activation in CAFs. In vivo, deletion of p38α in CAFs and glycogen phosphorylase inhibition in cancer cells reduced metastasis, suggesting that glycogen is an energy source used by cancer cells to facilitate metastatic tumor growth. et al show that ovarian cancer cells can mobilize glycogen as an energy source, leading to increased proliferation, invasion and metastasis, following their interaction with cancer-associated fibroblasts (CAFs). This process is dependent on p38α MAPK activation in CAFs and inhibition of the pathway reduced metastatic tumor growth in vivo.
登录
查看更多内容
影响因子：
4.8
作者：
Arrizabalaga, Onetsine;Lacerda, Hadriano M.;Zugaza, Jose L.
通讯作者：
Zugaza, Jose L.
影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
50.3
作者：
Hanahan, Douglas;Coussens, Lisa M.
通讯作者：
Coussens, Lisa M.
影响因子：
3
作者：
Carmen Louzao, M.;Espina, Begona;Botana, Luis M.
通讯作者：
Botana, Luis M.