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.

LINC complexes promote homologous recombination in part through inhibition of nonhomologous end joining

“…FA mutants exist for which the gene has not yet been identified, and it is possible that LINC inactivation could be the responsible lesion. Furthermore, the recent finding that SUN expression levels alter sensitivity to cisplatin treatment in lung cancers (Lv et al, 2015) suggests that manipulation of SUN may be an effective chemotherapy.…”

Histone deacetylase 7 inhibits plakoglobin expression to promote lung cancer cell growth and metastasis

“…Lung cancer is the leading cause of cancer-associated mortality worldwide (1,2), with an associated 5-year survival rate of <16% (3). Advancements in treatment have been made recently (4); however, the molecular mechanisms underlying the pathogenesis of lung cancer remain unknown.…”

NEK2 Promotes Aerobic Glycolysis in Multiple Myeloma Through Regulating Splicing of Pyruvate Kinase

“…The inhibition of Warburg effect deprives the generation of ATP, decreasing cancer cells growth and proliferation [10, 11]. Thus, Warburg effect has received substantial attention as a novel therapeutic target in cancers including lung cancer [12, 13], leukemia [14], breast cancer [15–18], pancreatic cancer [19, 20], colorectal cancer [21, 22], bladder cancer [23], and multiple myeloma [24, 25]. In multiple myeloma, dichloroacetate, which is an inhibitor of aerobic glycolysis, has been reported to increase myeloma cell sensitivity to bortezomib [24].…”