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

First Author  Goodwin ML Year  2014
Journal  Cancer Cell Volume  26
Issue  6 Pages  851-862
PubMed ID  25453902 Mgi Jnum  J:217462
Mgi Id  MGI:5614139 Doi  10.1016/j.ccell.2014.10.003
Citation  Goodwin ML, et al. (2014) Modeling alveolar soft part sarcomagenesis in the mouse: a role for lactate in the tumor microenvironment. Cancer Cell 26(6):851-62
abstractText  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.
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