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Updated: Sep 23, 2026
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
Lats2, a putative tumor suppressor, inhibits G1/S transition
Yunfang Li1, Jing Pei, Hong Xia
1Stem Cell Institute, Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Abstract:
Lats2 is a new member of the Lats tumor suppressor family. The human LATS2 gene is located at chromosome 13q11-12, which has been shown to be a hot spot (67%) for LOH in nonsmall cell lung cancer. In order to understand the function of LATS2 in the control of tumor development, we ectopically expressed mouse Lats2 via retroviral infection in NIH3T3/v-ras cells to examine whether Lats2 plays a role in suppressing tumor development and regulating cell proliferation. We have found that ectopic expression of Lats2 in NIH3T3/v-ras cells suppresses development of tumors in athymic nude mice and inhibits proliferation of NIH3T3/v-ras cells in an in vitro assay. Cell cycle profile analysis demonstrated that ectopic expression of Lats2 inhibited the G1/S transition. Further mechanistic studies revealed that cyclin E/CDK2 kinase activity was downregulated in Lats2-transduced NIH3T3/v-ras cells, while other cell cycle regulators controlling the G1/S transition were not affected. We have also shown that LATS2 kinase activity and two LATS conserved domains (LCDs) are required for Lats2 to suppress tumorigenicity and to inhibit cell growth. In addition, the LATS2 protein is cytoplasmic during interphase in NIH3T3 cells, while it becomes localized to the mitotic apparatus during mitosis. Finally, we propose a model in which a combination of mammalian Lats2 and Lats1 control cell proliferation by negatively regulating different cell cycle check points.
Insights
The Lats2 tumor suppressor inhibits NIH3T3/v-ras cell proliferation and tumor development by blocking the G1/S cell cycle transition. Its kinase activity and conserved domains are crucial for these tumor-suppressive functions.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Lats2 is a tumor suppressor gene implicated in cell cycle regulation.
- The LATS2 gene locus on chromosome 13q11-12 is frequently lost in non-small cell lung cancer.
- Understanding Lats2 function is critical for cancer research.
Purpose of the Study:
- To investigate the role of Lats2 in suppressing tumor development.
- To determine Lats2's effect on cell proliferation and the cell cycle.
- To elucidate the molecular mechanisms underlying Lats2's tumor-suppressive activity.
Main Methods:
- Ectopic expression of mouse Lats2 in NIH3T3/v-ras cells via retroviral infection.
- Tumorigenicity assays in athymic nude mice.
- In vitro cell proliferation assays and cell cycle analysis.
- Western blotting to assess cell cycle regulator activity (e.g., cyclin E/CDK2).
Main Results:
- Ectopic Lats2 expression suppressed tumor formation and inhibited NIH3T3/v-ras cell proliferation.
- Lats2 expression led to G1/S cell cycle arrest.
- Cyclin E/CDK2 kinase activity was downregulated, while other G1/S regulators remained unaffected.
- LATS2 kinase activity and its conserved domains (LCDs) were essential for its tumor-suppressive effects.
- LATS2 exhibited dynamic localization, shifting from the cytoplasm to the mitotic apparatus during mitosis.
Conclusions:
- Lats2 acts as a potent suppressor of tumor development and cell proliferation.
- Lats2 inhibits cell growth by downregulating cyclin E/CDK2 activity and blocking the G1/S transition.
- Lats2's tumor-suppressive functions depend on its kinase activity and conserved domains.
- Lats1 and Lats2 may cooperate to regulate cell proliferation through distinct cell cycle checkpoints.
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