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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
LATS tumor suppressor: a new governor of cellular homeostasis
1Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Abstract:
Accumulating evidence points to the LATS (Large Tumor Suppressor) family of human tumor suppressors (LATS1 and LATS2) as new resident governors of cellular homeostasis. Loss of function of either LATS1 or LATS2 leads to a variety of tumor types including soft tissue sarcomas, leukemia, as well as breast, prostate, lung and esophageal cancers. Due to their high degree of homology and functional overlap, LATS1 and LATS2 comprise a new tumor suppressor family. Classically identified within the Hippo-LATS signaling pathway, LATS also acts independently of this pathway, possessing multiple functions including regulation of cell proliferation, cell death and cell migration, as well as broad governing roles such as transcriptional regulation and maintenance of genetic stability. Activity of LATS is tightly controlled through various mechanisms including post-translational modifications, differential localization and expression. Although little is known about the specific underlying mechanisms of these activities, current data suggest that LATS signaling intersects with well-established tumor suppressive or oncogenic pathways including the p53, Ras or Akt networks. This review aims to identify what we know about the LATS tumor suppressor family, highlighting LATS1 and LATS2 redundancies and differences in terms of their structure, expression, regulation and functions, thereby establishing a novel tumor suppressor network.
Insights
The Large Tumor Suppressor (LATS) family, including LATS1 and LATS2, are crucial human tumor suppressors. Their dysfunction causes various cancers, highlighting their role in cellular homeostasis and a novel tumor suppressor network.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- Large Tumor Suppressor (LATS) proteins, LATS1 and LATS2, are key human tumor suppressors.
- Loss of LATS1 or LATS2 function is linked to diverse cancers, including sarcomas, leukemia, and breast, prostate, lung, and esophageal cancers.
- LATS1 and LATS2 exhibit high homology and functional overlap, defining them as a distinct tumor suppressor family.
Purpose of the Study:
- To review current knowledge on the LATS tumor suppressor family.
- To elucidate the redundancies and differences between LATS1 and LATS2 regarding structure, expression, regulation, and function.
- To establish a novel tumor suppressor network involving LATS proteins.
Main Methods:
- Literature review of existing studies on LATS1 and LATS2.
- Analysis of LATS protein structure, expression patterns, and regulatory mechanisms.
- Examination of LATS functions both within and independent of the Hippo-LATS signaling pathway.
Main Results:
- LATS proteins regulate cellular homeostasis, proliferation, cell death, and migration.
- LATS signaling intersects with established pathways like p53, Ras, and Akt.
- LATS activity is precisely controlled via post-translational modifications, localization, and expression levels.
Conclusions:
- LATS1 and LATS2 function as critical tumor suppressors with overlapping and distinct roles.
- Understanding LATS regulation and function is vital for comprehending cancer development.
- LATS proteins represent a novel network crucial for maintaining genetic stability and preventing tumorigenesis.
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