SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis

Tang, Xiaolong; Shi, Lei; Xie, Ni; Liu, Zuojun; Qian, Minxian; Meng, Fanbiao; Xu, Qing-Yang; Zhou, Mingyan; Cao, Xinyue; Zhu, Wei‐Guo; Liu, Baohua

doi:10.1038/s41467-017-00396-9

Cited by 188 publications

(185 citation statements)

References 70 publications

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“…Increasing evidence has indicated that EMT promotes breast cancer progression. Oncogenic pathways such as IL‐6/Stat3, TGF‐β/Smad3, Wnt and Notch are implicated in EMT‐associated breast cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

CD155 contributes to the mesenchymal phenotype of triple‐negative breast cancer

et al. 2020

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Patients with triple‐negative breast cancer (TNBC) lack molecular targets and have an unfavorable outcome. CD155 is overexpressed in human cancers, but whether it plays a role in TNBC is unexplored. Here we found that CD155 was enriched in both TNBC cell lines and tumor tissues. High CD155 expression was related to poor prognosis of breast cancer patients. CD155 was associated with a mesenchymal phenotype. CD155 knockdown induced a mesenchymal‐epithelial transition in TNBC cells, and suppressed TNBC cell migration, invasion and metastasis in vitro and in vivo. Mechanistically, CD155 cross‐talked with oncogenic IL‐6/Stat3 and TGF‐β/Smad3 pathways. Moreover, CD155 knockdown inhibited TNBC cell growth and survival. Taken together, these data indicate that CD155 contributes to the aggressive behavior of TNBC; targeting CD155 may be beneficial to these patients.

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Section: Introductionmentioning

confidence: 99%

CD155 contributes to the mesenchymal phenotype of triple‐negative breast cancer

et al. 2020

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“…Of the seven Sirtuin members, SIRT7 has remained the least understood. Only a handful of deacetylation targets have been reported, including p53, NRF1, GABP-␤1, H3K18ac, PAF53, U3-55K, and Smad4 (5)(6)(7)(8)(9)(10)(11). SIRT7 may have many more potential substrates according to a study using stable isotope labeling by amino acids in cell culture (SILAC)-coupled quantitative MS (12).…”

mentioning

confidence: 99%

“…It also selectively deacetylates H3K18Ac at the promoters of a network of genes with links to tumor suppression (6). Interestingly, SIRT7 is reported to be significantly down-regulated in breast cancer lung metastases in humans and mice and predicts metastasis-free survival (11). Much more remains to be explored regarding the role of SIRT7 in tumor progression.…”

mentioning

confidence: 99%

Sirtuin 7–mediated deacetylation of WD repeat domain 77 (WDR77) suppresses cancer cell growth by reducing WDR77/PRMT5 transmethylase complex activity

Shi

et al. 2018

Journal of Biological Chemistry

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The histone transmethylase complex comprising WD repeat domain 77 (WDR77) and protein arginine methyltransferase 5 (PRMT5) catalyzes dimethylation of H4R3 (H4R3me2) and drives cancer cell proliferation and migration, but its regulation is not fully understood. Here, we report that sirtuin 7 (SIRT7) directly deacetylates WDR77 and that this deacetylation interferes with the WDR77-PRMT5 interaction and suppresses proliferation of human colon cancer HCT116 cells. Using co-expression in HEK293T cells and co-immunoprecipitation assays, we observed that SIRT7 deacetylates WDR77 at Lys-3 and Lys-243, which reduced of WDR77's interaction with PRMT5. More importantly, this reduction suppressed the transmethylase activity of the WDR77/PRMT5 complex, resulting in a reduction of the H4R3me2 modification. Rescue of the WDR77-KO HCT116 cells with a WDR77-2KR (K3R and K243R) variant yielded cell migration and proliferation rates that were significantly lower than those of WDR77-KO HCT116 cells rescued with WT WDR77. In summary, SIRT7 is a major deacetylase for WDR77, and SIRT7-mediated deacetylation of WDR77 at Lys-3 and Lys-243 weakens the WDR77-PRMT5 interaction and activity and thereby suppresses growth of cancer cells.

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“…Tumor metastasis is usually associated with abnormal expression of cytokines, especially CXCL12 [42][43][44][45][46], VEGF [47,48], IL1β [49,50], and IL6 [51,52], while CAFs can promote tumor growth and invasion via a plethora of active factors [53]. We therefore checked these specific cytokines in different cancer cells with the presence or absence of different NF-CMs.…”

Section: Discussionmentioning

confidence: 99%

GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism

Shi

Song

et al. 2019

Cancer Gene Ther

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Tumorigenesis and metastasis depend on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. It is, however, unclear regarding the molecular mechanisms underlying the progress and metastasis of human clear-cell renal cell carcinoma in the microenvironment with fibroblasts. In this work, we investigated the effect of normal fibroblasts on the metastasis of renal cancer and the relevant signaling pathways. We isolated normal fibroblasts from normal renal tissues and used normal fibroblast-conditioned medium culture renal cancer cells. The CCK-8 and transwell assays showed that normal fibroblasts conditioned medium significantly enhanced ccRCC cell migration. IL6 mediated the cross talk between normal fibroblasts and the cancer cells, and promoted tumor cell migration through the STAT3 pathway. In contrast, GATA3 was downregulated at both mRNA and protein levels in the normal fibroblast-conditioned medium treated with renal cancer cells, but upregulated in adjacent normal tissues. GATA3 overexpression significantly reduced STAT3 phosphorylation and attenuated the migration in both renal cancer cell and IL6-stimulated renal cancer cell. Taken together, our findings suggest that the IL6/STAT3 pathway plays a crucial role in the normal fibroblast-enhanced clear-cell renal cell carcinoma metastasis, while GATA3 may mitigate this effect by inhibiting IL6/STAT3 signaling.

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SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis

Cited by 188 publications

References 70 publications

CD155 contributes to the mesenchymal phenotype of triple‐negative breast cancer

CD155 contributes to the mesenchymal phenotype of triple‐negative breast cancer

Sirtuin 7–mediated deacetylation of WD repeat domain 77 (WDR77) suppresses cancer cell growth by reducing WDR77/PRMT5 transmethylase complex activity

GATA3 suppresses human fibroblasts-induced metastasis of clear cell renal cell carcinoma via an anti-IL6/STAT3 mechanism

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