title: The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications.
abstract: BACKGROUND
  The incidence of lung cancers has increased globally. Increased exposure to tobacco, passive smoking, less consumption of vegetables and fruits and occupational exposure to asbestos, arsenic and chromium are the main risk factors. The pathophysiology of lung cancer is complex and not well understood. Various microRNAs, genes and pathways are associated with lung cancers. The genes involved in lung cancers produce proteins involved in cell growth, differentiation, different cell cycles, apoptosis, immune modulation, tumor spread and progression. The Hippo pathway (also known as the Salvador-Warts-Hippo pathway) is the latest emerging concept in cancers. The Hippo pathway plays an important role in controlling the size of the tissue and organ by virtue of its action on cell proliferation and apoptosis.
  
  
  OBJECTIVE
  In the present review, we highlight the mammalian Hippo pathway, role of its core members, its upstream regulators, downstream effectors and the resistance cases in lung cancers.
  
  
  RESULTS
  Specific interaction of Mer with cell surface hyaluronan receptor CD44 is vital in cell contact inhibition, thereby activating Hippo pathway. Both transcription co-activators YAP and TAZ (also known as WWTR1, being homologs of Drosophila Yki) are important regulators of proliferation and apoptosis, and serve as major downstream effectors of the Hippo pathway. Mutation of NF2, the upstream regulator of Hippo pathway is linked to the cancers.
  
  
  CONCLUSIONS
  Targeting YAP and TAZ may be important for future drug delivery and treatment.
authors.affiliation: Department of Anatomy, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia.
authors.forename: Seong Lin
authors.initials: SL
authors.lastname: Teoh
authors.affiliation: Department of Anatomy, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia.
authors.forename: Srijit
authors.initials: S
authors.lastname: Das
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis; D049109:Cell Proliferation; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D053263:Gene Regulatory Networks; D000090683:Hippo Signaling Pathway; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D000091102:YAP-Signaling Proteins; D000076202:c-Mer Tyrosine Kinase / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C097072:MERTK protein, human; D000076202:c-Mer Tyrosine Kinase; D017346:Protein Serine-Threonine Kinases
keywords: Cell proliferation; apoptosis; drug delivery; genes; hippo pathway; lung cancer