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Fibroblasts Mobilize Tumor Cell Glycogen to Promote Proliferation and Metastasis

机译:成纤维细胞调动肿瘤细胞糖原以促进增殖和转移

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摘要

Successful metastasis requires the co-evolution of stromal and cancer cells. We used stable isotope labeling of amino acids in cell culture 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, 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 p38 alpha MAPK activation in CAFs. In vivo, deletion of p38 alpha 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.
机译:成功的转移需要基质和癌细胞的共同演变。 我们使用稳定同位素标记在细胞培养中含有定量,无标记磷蛋白酶的氨基酸标记,以在共培养后研究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,根据常氧的条件与CAFS的相互作用支持甘氨酸溶解,并诱导磷酸血糖酶1的磷酸化和活化,其参与糖原代谢。 糖原汇集到糖酵解中,导致癌细胞与人CAF共同培养的癌细胞增殖,侵袭和转移增加。 癌细胞中的糖原动员依赖于CAFS中的P38αMapk活化。 在体内,在CAFS和糖原磷酸化酶中缺失P38α在癌细胞中降低转移,表明糖原是癌细胞使用的能源,以促进转移性肿瘤生长。

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  • 来源
    《Cell metabolism》 |2019年第1期|共24页
  • 作者单位

    Univ Chicago Dept Obstet &

    Gynecol Sect Gynecol Oncol Chicago IL 60637 USA;

    Univ Chicago Dept Obstet &

    Gynecol Sect Gynecol Oncol Chicago IL 60637 USA;

    Univ Chicago Dept Obstet &

    Gynecol Sect Gynecol Oncol Chicago IL 60637 USA;

    Univ Chicago Dept Obstet &

    Gynecol Sect Gynecol Oncol Chicago IL 60637 USA;

    Univ Chicago Dept Obstet &

    Gynecol Sect Gynecol Oncol Chicago IL 60637 USA;

    Univ Chicago Dept Obstet &

    Gynecol Sect Gynecol Oncol Chicago IL 60637 USA;

    Brown Univ Dept Mol Biol Cell Biol &

    Biochem Ctr Genom &

    Prote Providence RI 02903 USA;

    Barcelona Inst Sci &

    Technol IRB Barcelona Barcelona 08028 Spain;

    Duke Univ Duke Canc Inst Duke Mol Physiol Inst Dept Pharmacol &

    Canc Biol Sch Med Durham NC;

    Barcelona Inst Sci &

    Technol IRB Barcelona Barcelona 08028 Spain;

    Duke Univ Duke Canc Inst Duke Mol Physiol Inst Dept Pharmacol &

    Canc Biol Sch Med Durham NC;

    Univ Chicago Dept Obstet &

    Gynecol Sect Gynecol Oncol Chicago IL 60637 USA;

    Univ Chicago Dept Pathol Chicago IL 60637 USA;

    Univ Chicago Dept Pathol Chicago IL 60637 USA;

    Brown Univ Alpert Med Sch Div Biol &

    Med Providence RI 02903 USA;

    Duke Univ Duke Canc Inst Duke Mol Physiol Inst Dept Pharmacol &

    Canc Biol Sch Med Durham NC;

    Brown Univ Dept Mol Biol Cell Biol &

    Biochem Ctr Genom &

    Prote Providence RI 02903 USA;

    Barcelona Inst Sci &

    Technol IRB Barcelona Barcelona 08028 Spain;

    Univ Chicago Dept Obstet &

    Gynecol Sect Gynecol Oncol Chicago IL 60637 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 内分泌腺疾病及代谢病;
  • 关键词

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