Title:The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications
Volume: 18
Issue: 16
Author(s): Seong Lin Teoh and Srijit Das*
Affiliation:
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Kuala Lumpur,Malaysia
Keywords:
Cell proliferation, apoptosis, hippo pathway, lung cancer, genes, drug delivery.
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.
