Clinicopathological Significance of Large Tumor Suppressor (<i>LATS</i>) Expression in Gastric Cancer

Son, Myoung Won; Song, Geum Jong; Jang, Si‐Hyong; Hong, Sungguan; Oh, Mee‐Hye; Lee, Jihye; Baek, Moo Jun; Lee, Moon Soo

doi:10.5230/jgc.2017.17.e41

Cited by 9 publications

(12 citation statements)

References 23 publications

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“…Once the Hippo signaling pathway is activated, MST1 and MST2 induce LATS1/2 phosphorylation; then, LATS1/2 kinases promote the binding of YAP1 to 14-3-3 proteins by phosphorylation, resulting in YAP1 inactivation and entrapment in the cytoplasm [48,49]. Numerous studies have shown that the tumor suppressor LATS2 is downregulated in various carcinomas and that this protein impedes tumor proliferation and invasion, e.g., in GC [20], nonsmall cell lung cancer (NSCLC) [50,51] and ovarian tumors [52]. Our previous studies assessed YAP1, a downstream transcriptional co-activator, which is overexpressed in gastric carcinoma and closely correlated with progression, metastasis and poor patient prognosis [25,26].…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED ARTICLE: The novel long non-coding RNA LATS2-AS1-001 inhibits gastric cancer progression by regulating the LATS2/YAP1 signaling pathway via binding to EZH2

Sun

Wang

2020

Cancer Cell Int

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Background: To explore the expression pattern and role of the novel long non-coding RNA LATS2 antisense transcript 1 (LATS2-AS1-001) in gastric cancer (GC). Methods: qRT-PCR was applied to evaluate LATS2-AS1-001 expression and correlation with LATS2 in GC. In vitro experiments were performed to investigate the role of LATS2-AS1-001 in GC cells. RNA immunoprecipitation (RIP) was performed to assess the interaction between EZH2 and LATS2-AS1-001. LATS2/YAP1 signaling pathway proteins were detected by immunoblot. Oncomine and KMPLOT data analysis was conducted to assess the prognostic value of YAP1 in GC. Results: Decreased expression levels of LATS2-AS1-001 and LATS2 were confirmed in 357 GC tissues compared with the normal mucosa. A strong positive correlation between LATS2-AS1-001 and LATS mRNA expression was found in Pearson Correlation analysis (r = 0.719, P < 0.001). Furthermore, ROC curve analysis revealed areas under the curves for LATS2-AS1-001 and LATS2 of 0.7274 and 0.6865, respectively (P < 0.001), which indicated that LATS2-AS1-001 and LATS could be used as diagnostic indicators in GC. Moreover, ectopic expression of LATS2-AS1-001 decreased cell viability, induced G0/G1 phase arrest, and inhibited cell migration and invasion in GC cells. Mechanistically, overexpressing LATS2-AS1-001 upregulated LATS2 and induced YAP1 phosphorylation via binding to EZH2. Oncomine and KMPLOT database analysis demonstrated YAP1 was highly expressed in human GC samples, and high YAP1 expression predicted poor patient prognosis in GC. Conclusion: This study revealed that lncRNA LATS2-AS1-001 might serve as a potential diagnostic index in GC and act as a suppressor of GC progression.

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Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence indicates that antisense transcripts, especially non-coding RNAs, might regulate sense genes [19]. LATS2 expression is considered a good prognostic factor in GC [20]. Nevertheless, to the best of our knowledge, the expression and effects of LATS2-AS1-001 in human tumors have not been investigated to date.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The novel long non-coding RNA LATS2-AS1-001 inhibits gastric cancer progression by regulating the LATS2/YAP1 signaling pathway via binding to EZH2

Sun

Wang

2020

Cancer Cell Int

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“…They have been reported to govern cellular homeostasis by preventing cell proliferation and migration, by inducing cell death and senescence, and by regulating cell cycle checkpoints to maintain genetic stability (Visser and Yang 2010; Furth and Aylon 2017). Consistent with their proposed tumor-suppressive function, LATS proteins have been reported to be down-regulated in various cell types including breast cancer (Morinaga et al 2000), non-small lung cancer (Lin et al 2014), and gastric cancer (Son et al 2017). However, LATS was reported to be overexpressed in nasopharyngeal cancer (Zhang et al 2010), suggesting that the function of LATS remains controversial and may be tissue- and cancer-type dependent.…”

Section: Introductionmentioning

confidence: 83%

“…Clinically, LATS expression can have prognostic value. LATS1 and LATS2 expressions have been reported as significant markers for good prognosis in patients with gastric cancer (Son et al 2017), reduced LATS1 correlated with poor outcome with breast cancer patients (Takahashi et al 2005), and reduced LATS2 correlated with poor survival in acute lymphoblastic leukemia (Jiménez-Velasco et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Outcome in serous ovarian cancer is not associated with LATS expression

Montavon

Stricker

Schoetzau

et al. 2019

J Cancer Res Clin Oncol

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BackgroundLarge tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer.Materials and methodsWe analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay).ResultsThe analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity.ConclusionThese results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.

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“…Large tumor suppressor kinases 1/2 (LATS1/2) are core members of the Hippo pathway, and their activation is the major functional output of this pathway. LATS1 and LATS2 have the same function and are both expressed in GC ( 9 , 10 ). Although LATS1/2 are traditionally believed to inhibit tumor growth ( 11 , 12 ), Pan et al found that LATS1/2 deletion inhibits the growth of murine MC38 colon cancer cells ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Role of LATS1/2 in Prognosis of Advanced Gastric Cancer and Its Relationship With the Tumor Immune Microenvironment

Guo

Liu

et al. 2020

Front. Oncol.

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Background: Gastric cancer (GC) remains a refractory cancer particularly in Eastern Asia. Large tumor suppressor kinases 1/2 (LATS1/2) are core members of the Hippo pathway. The role of LATS1/2 in the prognosis of different subtypes of advanced gastric cancer and its relationship with the tumor immune microenvironment in GC remain unknown. Exploring the role of LATS1/2 in GC might provide potential immunotherapeutic approaches for treating GC. Methods: Four hundred and ninety surgically resected primary GC samples were assessed for LATS1/2, CD8, FOXP3, and CD163. Correlations between LATS1/2 expression and immune-related markers were investigated and the prognoses of patients with different GC subtypes were analyzed. Results: CD8 and CD163 appeared to be favorable and adverse prognostic factors, respectively. LATS1/2 and FOXP3 did not predict patients' overall survival. However, in microsatellite-stable GC patients, high LATS1/2 and FOXP3 expression and low CD8 expression predicted poor prognoses. Furthermore, high LATS1/2 expression was significantly correlated with decreased CD8 and increased FOXP3. Combined analysis of LATS1/2, CD8, and FOXP3 had better prognostic accuracy than did each marker individually. Conclusions: Different biological molecules can predict the prognoses of different types of GC patients. LATS1/2, core kinases in the Hippo pathway, are closely related to CD8 and FOXP3. Further understanding the mechanisms of LATS1/2 in CD8 + T cells and FOXP3 + Treg cells provides further theoretical basis and potential targets for GC immunotherapy.

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Clinicopathological Significance of Large Tumor Suppressor (LATS) Expression in Gastric Cancer

Cited by 9 publications

References 23 publications

RETRACTED ARTICLE: The novel long non-coding RNA LATS2-AS1-001 inhibits gastric cancer progression by regulating the LATS2/YAP1 signaling pathway via binding to EZH2

RETRACTED ARTICLE: The novel long non-coding RNA LATS2-AS1-001 inhibits gastric cancer progression by regulating the LATS2/YAP1 signaling pathway via binding to EZH2

Outcome in serous ovarian cancer is not associated with LATS expression

Role of LATS1/2 in Prognosis of Advanced Gastric Cancer and Its Relationship With the Tumor Immune Microenvironment

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