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SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer.

ABSTRACT: SUN2, a key component of LINC (linker of nucleoskeleton and cytoskeleton) complex located at the inner nuclear membrane, plays unknown role in lung cancer. We found that SUN2 expression was decreased in lung cancer tissue compared with paired normal tissues and that higher SUN2 levels predicted better overall survival and first progression survival. Overexpression of SUN2 inhibits cell proliferation, colony formation and migration in lung cancer, whereas knockdown of SUN2 promotes cell proliferation and migration. Additionally, SUN2 increases the sensitivity of lung cancer to cisplatin by inducing cell apoptosis. Mechanistically, we showed that SUN2 exerts its tumor suppressor functions by decreasing the expression of GLUT1 and LDHA to inhibit the Warburg effect. Finally, our results provided evidence that SIRT5 acts, at least partly, as a negative regulator of SUN2.Taken together, our findings indicate that SUN2 is a key component in lung cancer progression by inhibiting the Warburg effect and that the novel SIRT5/SUN2 axis may prove to be useful for the development of new strategies for treating the patients with lung cancer.

SUBMITTER: Lv XB

PROVIDER: S-EPMC4674702 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer.

Lv Xiao-bin XB Liu Lijuan L Cheng Chun C Yu Bentong B Xiong Longxin L Hu Kaishun K Tang Jianjun J Zeng Lei L Sang Yi Y

Scientific reports 20151210

SUN2, a key component of LINC (linker of nucleoskeleton and cytoskeleton) complex located at the inner nuclear membrane, plays unknown role in lung cancer. We found that SUN2 expression was decreased in lung cancer tissue compared with paired normal tissues and that higher SUN2 levels predicted better overall survival and first progression survival. Overexpression of SUN2 inhibits cell proliferation, colony formation and migration in lung cancer, whereas knockdown of SUN2 promotes cell prolifera ...[more]

PMID: 26658802

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Project description:BackgroundDespite advances in prognosis and treatment of lung adenocarcinoma (LADC), a notable non-small cell lung cancer subtype, patient outcomes are still unsatisfactory. New insight on novel therapeutic strategies for LADC may be gained from a more comprehensive understanding of cancer progression mechanisms. Such strategies could reduce the mortality and morbidity of patients with LADC. In our previous study, we performed cDNA microarray screening and found an inverse relationship between inhibitor of DNA binding 2 (Id2) expression levels and the invasiveness of LADC cells.Materials and methodsTo identify the functional roles of Id2 and its action mechanisms in LADC progression, we successfully established several Id2-overexpressing and Id2-silenced LADC cell clones. Subsequently, we examined in vitro the effects exerted by Id2 on cell morphology, proliferation, colony formation, invasive, and migratory activities and examined in vivo those exerted by Id2 on cell metastasis. The mechanisms underlying the action of Id2 were investigated using RNA-seq and pathway analyses. Furthermore, the correlations of Id2 with its target gene expression and clinical outcomes were calculated.ResultsOur data revealed that Id2 overexpression could inhibit LADC cells' migratory, invasive, proliferation, and colony formation capabilities. Silencing Id2 expression in LADC cells reversed the aforementioned inhibitory effects, and knockdown of Id2 increased LADC cells' metastatic abilities in vivo. Bioinformatics analysis revealed that these effects of Id2 on cancer progression might be regulated by focal adhesion kinase (FAK) signaling and CD44/Twist expression. Furthermore, in online clinical database analysis, patients with LADC whose Id2 expression levels were high and FAK/Twist expression levels were low had superior clinical outcomes.Conclusion: Our data indicate that the Id2 gene may act as a metastasis suppressor and provide new insights into LADC progression and therapy.

Dataset Information

SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer.

Publications

SUN2 exerts tumor suppressor functions by suppressing the Warburg effect in lung cancer.

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