The Hippo signal transduction pathway in soft tissue sarcomas

Abdalla D Mohamed, Annie M Tremblay, Graeme I Murray, Henning Wackerhage

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20 Citations (Scopus)

Abstract

Sarcomas are rare cancers (≈1% of all solid tumours) usually of mesenchymal origin. Here, we review evidence implicating the Hippo pathway in soft tissue sarcomas. Several transgenic mouse models of Hippo pathway members (Nf2, Mob1, LATS1 and YAP1 mutants) develop various types of sarcoma. Despite that, Hippo member genes are rarely point mutated in human sarcomas. Instead, WWTR1-CAMTA1 and YAP1-TFE3 fusion genes are found in almost all cases of epithelioid haemangioendothelioma. Also copy number gains of YAP1 and other Hippo members occur at low frequencies but the most likely cause of perturbed Hippo signalling in sarcoma is the cross-talk with commonly mutated cancer genes such as KRAS, PIK3CA, CTNNB1 or FBXW7. Current Hippo pathway-targeting drugs include compounds that target the interaction between YAP and TEAD interaction, G-protein coupled receptors (GPCR) and the mevalonate pathway (e.g. statins). Given that many Hippo pathway-modulating drugs are already used in patients, this could lead to early clinical trials testing their efficacy in different types of sarcoma.

Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalBiochimica et Biophysica Acta
Volume1856
Issue number1
Early online date4 Jun 2015
DOIs
Publication statusPublished - 1 Aug 2015

Keywords

  • sarcoma
  • rhabdomyosarcoma
  • hippo pathway
  • YAP
  • TAZ
  • fusion genes

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    Mohamed, A. D., Tremblay, A. M., Murray, G. I., & Wackerhage, H. (2015). The Hippo signal transduction pathway in soft tissue sarcomas. Biochimica et Biophysica Acta, 1856(1), 121-129. https://doi.org/10.1016/j.bbcan.2015.05.006