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Norway

PMID:25453902  

Modeling alveolar soft part sarcomagenesis in the mouse: a role for lactate in the tumor microenvironment.

Matthew L Goodwin | Huifeng Jin | Krystal Straessler | Kyllie Smith-Fry | Ju-Fen Zhu | Michael J Monument | Allie Grossmann | R Lor Randall | Mario R Capecchi | Kevin B Jones
Cancer cell | 2014

Alveolar soft part sarcoma (ASPS), a deadly soft tissue malignancy with a predilection for adolescents and young adults, associates consistently with t(X;17) translocations that generate the fusion gene ASPSCR1-TFE3. We proved the oncogenic capacity of this fusion gene by driving sarcomagenesis in mice from conditional ASPSCR1-TFE3 expression. The completely penetrant tumors were indistinguishable from human ASPS by histology and gene expression. They formed preferentially in the anatomic environment highest in lactate, the cranial vault, expressed high levels of lactate importers, harbored abundant mitochondria, metabolized lactate as a metabolic substrate, and responded to the administration of exogenous lactate with tumor cell proliferation and angiogenesis. These data demonstrate lactate's role as a driver of alveolar soft part sarcomagenesis.

Pubmed ID: 25453902

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: K08CA138764
  • Agency: NCI NIH HHS, United States
    Id: P30CA042014
  • Agency: NCI NIH HHS, United States
    Id: R01 CA210165
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007464
  • Agency: NCI NIH HHS, United States
    Id: K08 CA138764
  • Agency: NCI NIH HHS, United States
    Id: P30 CA042014

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DESeq (tool)

RRID:SCR_000154

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on August 30,2023. Software for differential gene expression analysis based on the negative binomial distribution. It estimates variance-mean dependence in count data from high-throughput sequencing assays and tests for differential expression.

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