SIRT1 enhances matrix metalloproteinase‐2 expression and tumor cell invasion in prostate cancer cells

Lovaas, Jenna D.; Zhu, Lijia; Chiao, Chi; Byles, Vanessa; Faller, Douglas V.; Dai, Yan

doi:10.1002/pros.22592

Cited by 58 publications

(32 citation statements)

References 29 publications

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“…These results indicated the positive role of SIRT1 in the genesis and the development of cancer, and are consistent with previous findings on several cancers showing that the upregulation of SIRT1 plays a role in tumorigenesis. 23,24 The oncogenic aspect of SIRT1 was explained previously by Cheng et al, 25 that is, P53 acetylation and apoptosis were enhanced in SIRT1-deficient mice, which is in line with the hypothesis that SIRT1 deacetylates P53, thereby inhibiting its tumor-suppressive function. Furthermore, the inhibition of SIRT1 by Sirtinol was shown to cause senescence-like cell growth arrest in lung and breast cancer, 26 and the SIRT1-selective inhibitor EX527 produced compelling findings for cancer management.…”

Section: Discussionsupporting

confidence: 60%

Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma

Mvunta

Miyamoto²,

Asaka³

et al. 2017

Applied Immunohistochemistry &Amp; Molecular Morphology

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Sirtuin 1 (SIRT1), originally identified as a longevity gene, regulates DNA repair and metabolism by deacetylating target proteins such as p53. SIRT1 plays a key role in the pathophysiology of metabolic diseases and neurodegenerative disorders, and is considered to protect against age-related diseases including cancer. In contrast, SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the expression and the role of SIRT1 in ovarian carcinoma (OvCa). The expression of SIRT1 was evaluated immunohistochemically in 16 cases of normal ovaries, 35 cases of endometriosis with/without carcinoma, and 68 cases of OvCa (endometrioid, 16; clear cell, 20; mucinous, 16; serous, 16). Staining results were evaluated semiquantitatively by the Immunoreactive Scoring System, and the relationships with clinicopathologic features and outcomes of patients were analyzed. The expression of SIRT1 was higher in endometrioid, mucinous, and clear-cell carcinomas than in the inclusion cysts of normal ovaries, but not in serous carcinoma (P=0.038). The expression of SIRT1 on OvCa did not correlate with age, stage, location of metastasis, or capsular penetration. However, elevated SIRT1 expression was a significant predictor of shorter survival in univariate (P=0.038) and multivariate (P=0.037) survival analyses, regardless of the tumor stage. Results of the present study suggest a positive role for SIRT1 in the development of OvCa and its potential as a novel therapeutic target.

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Section: Discussionsupporting

confidence: 60%

Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma

Mvunta

Miyamoto²,

Asaka³

et al. 2017

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…To further confirm the TSP-2 expression levels on PCa progression in vivo, the samples from the different stages of PCa patients were collected. Enormous studies have indicated the crucial roles of MMP-2 in PCa prognostic significance progression [28, 29]. Therefore, we assessed the correlation between TSP-2 and MMP-2 expression in PCa specimens.…”

Section: Resultsmentioning

confidence: 99%

Thrombospondin-2 promotes prostate cancer bone metastasis by the up-regulation of matrix metalloproteinase-2 through down-regulating miR-376c expression

et al. 2017

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BackgroundThrombospondin-2 (TSP-2) is a secreted matricellular glycoprotein that is found to mediate cell-to-extracellular matrix attachment and participates in many physiological and pathological processes. The expression profile of TSP-2 on tumors is controversial, and it up-regulates in some cancers, whereas it down-regulates in others, suggesting that the functional role of TSP-2 on tumors is still uncertain.MethodsThe expression of TSP-2 on prostate cancer progression was determined in the tissue array by the immunohistochemistry. The molecular mechanism of TSP-2 on prostate cancer (PCa) metastasis was investigated through pharmaceutical inhibitors, siRNAs, and miRNAs analyses. The role of TSP-2 on PCa metastasis in vivo was verified through xenograft in vivo imaging system.ResultsBased on the gene expression omnibus database and immunohistochemistry, we found that TSP-2 increased with the progression of PCa, especially in metastatic PCa and is correlated with the matrix metalloproteinase-2 (MMP-2) expression. Additionally, through binding to CD36 and integrin ανβ3, TSP-2 increased cell migration and MMP-2 expression. With inhibition of p38, ERK, and JNK, the TSP-2-induced cell migration and MMP-2 expression were abolished, indicating that the TSP-2’s effect on PCa is MAPK dependent. Moreover, the microRNA-376c (miR-376c) was significantly decreased by the TSP-2 treatment. Furthermore, the TSP-2-induced MMP-2 expression and the subsequent cell motility were suppressed upon miR-376c mimic stimulation. On the other hand, the animal studies revealed that the bone metastasis was abolished when TSP-2 was stably knocked down in PCa cells.ConclusionsTaken together, our results indicate that TSP-2 enhances the migration of PCa cells by increasing MMP-2 expression through down-regulation of miR-376c expression. Therefore, TSP-2 may represent a promising new target for treating PCa.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0390-6) contains supplementary material, which is available to authorized users.

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“…An overexpression of nicotinamide phosphoribosyltransferase in PCa cells along with SIRT1 leads to oxidative stress resistance. 43 Moreover, SIRT1 promotes both cell invasion in PCa cells enhancing matrix metalloproteinase-2, which has been shown to play an important role in cancer cell invasion, 44 and induction of epithelialto-mesenchymal transition through the promotion of the transcription factor ZEB1. 45 However, the current studies demonstrate reduced SIRT1 levels in patients with PCa are associated with reduced recurrence-free survival in human PCa.…”

Section: Discussionmentioning

confidence: 99%

Loss of Sirt1 Promotes Prostatic Intraepithelial Neoplasia, Reduces Mitophagy, and Delays Park2 Translocation to Mitochondria

Sante

Pestell

Casimiro

et al. 2015

The American Journal of Pathology

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Prostatic intraepithelial neoplasia is a precursor to prostate cancer. Herein, deletion of the NAD(+)-dependent histone deacetylase Sirt1 induced histological features of prostatic intraepithelial neoplasia at 7 months of age; these features were associated with increased cell proliferation and enhanced mitophagy. In human prostate cancer, lower Sirt1 expression in the luminal epithelium was associated with poor prognosis. Genetic deletion of Sirt1 increased mitochondrial superoxide dismutase 2 (Sod2) acetylation of lysine residue 68, thereby enhancing reactive oxygen species (ROS) production and reducing SOD2 activity. The PARK2 gene, which has several features of a tumor suppressor, encodes an E3 ubiquitin ligase that participates in removal of damaged mitochondria via mitophagy. Increased ROS in Sirt1(-/-) cells enhanced the recruitment of Park2 to the mitochondria, inducing mitophagy. Sirt1 restoration inhibited PARK2 translocation and ROS production requiring the Sirt1 catalytic domain. Thus, the NAD(+)-dependent inhibition of SOD2 activity and ROS by SIRT1 provides a gatekeeper function to reduce PARK2-mediated mitophagy and aberrant cell survival.

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SIRT1 enhances matrix metalloproteinase‐2 expression and tumor cell invasion in prostate cancer cells

Cited by 58 publications

References 29 publications

Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma

Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma

Thrombospondin-2 promotes prostate cancer bone metastasis by the up-regulation of matrix metalloproteinase-2 through down-regulating miR-376c expression

Loss of Sirt1 Promotes Prostatic Intraepithelial Neoplasia, Reduces Mitophagy, and Delays Park2 Translocation to Mitochondria

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