Related Experiment Video

Updated: Mar 11, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.8K

The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity

Toshiro Moroishi1, Tomoko Hayashi2, Wei-Wei Pan3

  • 1Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.

Cell
|December 3, 2016
PubMed

Insights

The Hippo pathway, specifically large tumor suppressor 1 and 2 (LATS1/2) kinases, unexpectedly suppresses anti-tumor immunity. Inhibiting LATS1/2 enhances immune responses, leading to tumor regression and improved cancer vaccine efficacy.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Tumor cells with poor immunogenicity evade host immune surveillance, contributing to cancer progression.
  • The intricate mechanisms governing tumor immunogenicity remain incompletely understood.
  • The Hippo pathway's role in regulating anti-tumor immunity is largely unexplored.

Purpose of the Study:

  • To investigate the role of the Hippo pathway in regulating anti-tumor immunity.
  • To determine if targeting the Hippo pathway can enhance anti-tumor immune responses.
  • To explore the potential of LATS1/2 as a therapeutic target in cancer immunotherapy.

Main Methods:

  • Utilized three murine syngeneic tumor models (B16, SCC7, 4T1).
  • Assessed the impact of deleting large tumor suppressor 1 and 2 (LATS1/2) kinases in tumor cells.
  • Investigated the role of adaptive immune responses and extracellular vesicle secretion.
  • Analyzed the Toll-like receptors-MYD88/TRIF pathway activation.

Main Results:

  • Loss of LATS1/2 in tumor cells significantly inhibited tumor growth across all models.
  • Tumor regression resulting from LATS1/2 deletion was dependent on adaptive immune responses.
  • LATS1/2 deficiency enhanced the efficacy of tumor vaccines.
  • LATS1/2-null tumor cells secreted extracellular vesicles that induced type I interferon responses.

Conclusions:

  • The Hippo pathway, through LATS1/2 kinases, plays a critical role in suppressing anti-tumor immunity.
  • Targeting LATS1/2 can enhance tumor immunogenicity and promote immune-mediated tumor destruction.
  • Inhibition of LATS1/2 represents a promising strategy for cancer immunotherapy.
Keywords:
B16 melanomaHippoLATSTAZToll-like receptorYAPcancer immunityexosomeimmunotherapyinterferon

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.8K
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

8.0K

Related Concept Videos

Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.0K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
10.1K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.0K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.5K