The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications

Our plain-English summary of The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications, by S.L. Teoh, S. Das (Current Drug Targets, 2017).

The study

• Authors: S.L. Teoh, S. Das
• Journal: Current Drug Targets
• Published: 2017;18(16):1880-1892
• Type of article: Review
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

Conclusion: Targeting YAP and TAZ may be important for future drug delivery and treatment.

Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

In plain English

This article was a narrative review, not a new study. The authors, from Universiti Kebangsaan Malaysia Medical Centre, summarized published research on the Hippo pathway (a set of proteins in cells that helps control cell growth and cell death) and its role in lung cancers. Asbestos appeared only in the background, listed with tobacco, chromium and arsenic as risk factors for lung cancer. The review did not examine asbestos exposure. Citing earlier studies, the authors wrote that the proteins YAP and TAZ were key regulators of cell growth and cell death. They wrote that the interaction of the protein Merlin with CD44 may be important in switching the pathway on, and that mutation of the NF2 gene had been detected in mesotheliomas. They described laboratory studies in which higher TAZ and YAP levels were linked to resistance to the lung cancer drugs gefitinib and erlotinib. They also reviewed possible drugs such as verteporfin, noting that one study found it inhibited tumor growth by a mechanism independent of its effects on YAP and TAZ. The authors concluded that targeting YAP and TAZ may be important for future drug treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published research. It reports no new data of its own.
• Who was studied: No study population. The authors reviewed published studies on the mammalian Hippo pathway in lung cancers, including non-small cell and small cell lung cancer tissue, lung cancer cell lines and mouse models.
• Exposure: No asbestos exposure was studied. Asbestos was mentioned only in the background, alongside chromium and arsenic, as an occupational risk factor for lung cancer. Citing another source, the article states that about 2 to 9% of lung cancers are due to occupational exposure.
• Main results:
  • From cited studies: the transcription co-activators YAP and TAZ are key regulators of cell proliferation and apoptosis and are the main downstream effectors of the Hippo pathway.
  • From a cited study: the interaction of Merlin (the NF2 gene product) with the cell-surface receptor CD44 may be important in cell contact inhibition, thereby activating the Hippo pathway.
  • From cited studies: NF2 mutation, linked to central nervous system tumors, was also detected in mesotheliomas. The article does not specify the type of mesothelioma.
  • From a cited study on resistance to EGFR-targeted drugs: the relative level of TAZ mRNA in a gefitinib-resistant cell line was 2.84-fold higher than in gefitinib-sensitive cells.
  • From cited studies: verteporfin was identified as an inhibitor of the YAP-TEAD interaction. However, another study found that verteporfin inhibited tumor growth by impairing the clearance of oligomerized proteins, a mechanism independent of its effects on YAP/TAZ.
• The authors' conclusion: The authors concluded that targeting YAP and TAZ may be important for future drug delivery and treatment of lung cancers.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Occupational Exposure, Apoptosis.

Related studies

• How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations — H. Rehrauer, L. Wu, et al. (2018)
• Hippo pathway gene mutations in malignant mesothelioma: revealed by RNA and targeted exon sequencing — A. Miyanaga, M. Masuda, et al. (2015)
• TAZ activation by Hippo pathway dysregulation induces cytokine gene expression and promotes mesothelial cell transformation — A. Matsushita, T. Sato, et al. (2019)
• Immunohistochemistry for NF2, LATS1/2, and YAP/TAZ Fails to Separate Benign From Malignant Mesothelial Proliferations — B.S. Sheffield, J. Lorette, et al. (2016)
• LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade — I. Tanaka, H. Osada, et al. (2015)
• The hippo pathway provides novel insights into lung cancer and mesothelioma treatment — X.L. Liu, R. Zuo, et al. (2018)

Browse more research in Current Drug Targets, or return to medical research.