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The Role of Twist1 Phosphorylation in Tumor Angiogenesis in Lung Cancer
Author(s) -
Mammoto Tadanori,
Jiang Amanda,
Jiang Elisabeth,
Mammoto Akiko
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.439.4
Subject(s) - angiogenesis , lung cancer , cancer research , medicine , neovascularization , cancer , phosphorylation , lung , vascular endothelial growth factor , pathology , immunology , biology , microbiology and biotechnology , vegf receptors
Lung cancer is the leading cause of cancer death in the US and the survival rate for advanced lung cancer patients is very low. Deregulated angiogenesis ‐the formation of new blood capillaries from existing blood vessels‐ contributes to lung cancer; however, current anti‐angiogenic therapy has potential problems such as rebound tumor growth and resistance to therapy. Here we implant fibrin gel containing either lung tumor‐derived factors or a small pellet of lung cancer cells on the mouse lung and show that a transcription factor, Twist1, mediates tumor angiogenesis through the VEGF‐VEGFR2 pathway. Conditioned media from lung cancer cells upregulate Twist1 Ser42 phosphorylation in endothelial cells (ECs), and Twist1 knockdown or inhibition of Twist1 Ser42 phosphorylation using a mutant construct (Twist1S42A) decreases VEGFR2 expression and EC sprouting induced by conditioned media in vitro. Tumor angiogenesis is also inhibited in fibrin gel implanted on Tie2‐specific Twist1 conditional knockout mouse lungs or Twist1S42A‐treated mouse lungs in vivo . These results suggest that Twist1 Ser42 phosphorylation plays a key role in tumor angiogenesis associated with lung cancer, and modulation of Twist1 Ser42 phosphorylation could be a potential therapeutic strategy for lung cancer. Support or Funding Information Boston Children's Hospital Career Development Award