NTRK1 is a positive regulator of YAP oncogenic function

Oncogene. 2019 Apr;38(15):2778-2787. doi: 10.1038/s41388-018-0609-1. Epub 2018 Dec 12.


Multiple cancer signalling networks take part in regulatory crosstalks with the Hippo tumour suppressor pathway through the transcriptional cofactor Yes-associated protein (YAP). Nevertheless, how YAP is controlled by pathway crosstalks in tumourigenesis remains poorly understood. Here, we performed a targeted kinase inhibitor screen in human cancer cells to identify novel Hippo pathway regulators. Notably, we identified the nerve growth factor (NGF) receptor tyrosine kinase (NTRK1), a molecule not previously associated with Hippo signalling. NTRK1 inhibition decreased YAP-driven transcription, cancer cell proliferation and migration. Furthermore, using a complementary functional genomics approach and mouse xenograft models, we show that NTRK1 regulates YAP oncogenic activity in vivo. Mechanistically, NTRK1 inhibition was found to induce large suppressor kinase 1 (LATS1) phosphorylation and to control YAP subcellular localization. Taken together, these results provide compelling evidence of crosstalks between the NGF-NTRK1 and Hippo cancer pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Carcinogenesis / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Oncogenes / genetics*
  • Phosphoproteins / genetics*
  • Phosphorylation / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Receptor, trkA / genetics*
  • Signal Transduction / genetics
  • Transcription Factors
  • Transcription, Genetic / genetics
  • YAP-Signaling Proteins


  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Receptor, trkA
  • Protein Serine-Threonine Kinases