Anti-tumor effect of LATS2 on liver cancer death: Role of DRP1-mediated mitochondrial division and the Wnt/β-catenin pathway.

08:00 EDT 10th April 2019 | BioPortfolio

Summary of "Anti-tumor effect of LATS2 on liver cancer death: Role of DRP1-mediated mitochondrial division and the Wnt/β-catenin pathway."

Large tumor suppressor 2 (LATS2), an important mediator of the cell apoptotic response pathway, has been linked to the progression of several cancers. Here, we described the molecular feature of LATS2 as a novel antitumor factor in liver cancer cells in vitro. Western blotting was used to detect the expression of LATS2 and its downstream factors. ELISA, immunofluorescence, and flow cytometry were used to evaluate the alterations of mitochondrial function in response to LATS2 overexpression. Adenovirus-loaded LATS2 and siRNA against DRP1 were transfected into liver cancer cells to overexpress LATS2 and knockdown DRP1 expression, respectively. The results of the present study demonstrated that overexpression of LATS2 was closely associated with more liver cancer cell death. Mechanistically, LATS2 overexpression increased the expression of DRP1, and DRP1 elevated mitochondrial division, an effect that was accompanied by mitochondrial dysfunction, including mitochondrial membrane potential reduction, mitochondrial respiratory complex downregulation, mitochondrial cyt-c release into the nucleus and mitochondrial oxidative injury. Moreover, LATS2 overexpression also initiated mitochondrial apoptosis, and this process was highly dependent on DRP1-related mitochondrial division. Molecular investigations demonstrated that LATS2 modulated DRP1 expression via the Wnt/β-catenin pathway. Inhibition of the Wnt/β-catenin pathway pregented LATS2-mediated DRP1 upregulation, ultimately sustaining mitochondrial function and cell viability in the presence of LATS2 overexpression. Altogether, the above data identify LATS2-Wnt/β-catenin/DRP1/mitochondrial division as a novel anticancer signaling pathway promoting cancer cell death, which might be an attractive therapeutic target for the treatment of hepatocellular carcinoma.


Journal Details

This article was published in the following journal.

Name: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
ISSN: 1950-6007
Pages: 108825


DeepDyve research library

PubMed Articles [44622 Associated PubMed Articles listed on BioPortfolio]

Large tumor suppressor 2, LATS2, activates JNK in a kinase-independent mechanism through ASK1.

Apoptosis signal-regulating kinase 1 (ASK1) is an important mediator of the cell stress response pathways. Because of its central role in regulating cell death, the activity of ASK1 is tightly regulat...

LATS2 inhibits cell proliferation and metastasis through the Hippo signaling pathway in glioma.

As a core kinase in the Hippo pathway, large tumor suppressor kinase 2 (LATS2) regulates cell proliferation, migration and invasion through numerous signaling pathways. However, its functions on cell ...

Isoliquiritigenin suppresses the proliferation and induced apoptosis via miR-32/LATS2/Wnt in nasopharyngeal carcinoma.

Nasopharyngeal Carcinoma is limited by the various severe side-effects and surgery is rarely performed. Iosliquiritigenin has a series of biological activities, such as antiviral, anti-free radical an...

Citron kinase interacts with LATS2 and inhibits its activity by occluding its hydrophobic phosphorylation motif.

The inhibitory effect of large tumor suppressor kinase (LATS1/2) on the activity of the oncoprotein yes-associated protein (YAP) is crucial to maintain tissue homeostasis. Proteomic studies have ident...

LATS2 Inhibits Malignant Behaviors of Glioma Cells via Inactivating YAP.

We previously reported that LATS2, the upstream serine/threonine kinase of Yes-associated protein (YAP), is downregulated in gliomas and exhibits negative correlation with the prognosis of glioma pati...

Clinical Trials [28362 Associated Clinical Trials listed on BioPortfolio]

Study of NS-9 in Patients With Liver Metastases

This study is to investigate the safety of NS-9 and to see how well it is tolerated in patients with cancer that has metastasized (spread) to the liver from another primary tumor. NS-9 is...

TSR-022 (Anti-TIM-3 Antibody) and TSR-042 (Anti-PD-1 Antibody) in Patients With Liver Cancer

TSR-022 and TSR-042 may stop the growth of tumor cells by allowing the immune system to attack the cancer. This phase II trial is studying how well TSR-022 and TSR-044 work in combination ...

A Phase I Study of Pazopanib in Adult Patients With Liver Cancer

Liver cancer is a good target for anti-angiogenic treatments such as pazopanib. The effect of pazopanib in patients with liver cancer are unknown. This study is designed to evaluate the ...

Genetic Analysis of Liver Cancer

Liver cancer is a leading cause of cancer deaths worldwide. While the molecular pathogenesis of liver cancer has been extensively studied, less is known about how the molecular biology of ...

A Study of the Safety and Antitumoral Efficacy of Nivolumab After SIRT for the Treatment of Patients With HCC

The purpose of this study is to evaluate the effect of the anti-programmed death 1 (PD-1) agent nivolumab following selective internal radiation therapy (SIRT) for patients with unresectab...

Medical and Biotech [MESH] Definitions

A tumor, basically a carcinoma with a single sarcoma such as leiomyosarcoma or angiosarcoma or multiple sarcomas of uterine origin. The role of estrogen has been postulated as a possible etiological factor in this tumor. (Holland et al., Cancer Medicine, 3d ed, p1703)

Liver disease lasting six months or more, caused by an adverse drug effect. The adverse effect may result from a direct toxic effect of a drug or metabolite, or an idiosyncratic response to a drug or metabolite.

A tumor necrosis factor receptor subtype with specificity for TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 15. It is found in tissues containing LYMPHOCYTES and may play a role in regulating lymphocyte homeostasis and APOPTOSIS. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.

An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.

An inhibitory B7 antigen that contains V-type and C2 type immunoglobulin domains. It has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN and provides negative signals that control and inhibit T-cell responses. It is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.

Quick Search


DeepDyve research library

Relevant Topics

Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Searches Linking to this Article