Distinct effects of SIRT1 in cancer and stromal cells on tumor promotion

Dong Hoon Shin, Yong Joon Choi, Peng Jin, Haejin Yoon, Yang Suk Chun, Hyunwoo Shin, Ja Eun Kim, Jong-Wan Park

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

The lysyl deacetylase SIRT1 acts as a metabolic sensor in adjusting metabolic imbalance. To explore the role of SIRT1 in tumor-stroma interplay, we designed an in vivo tumor model using SIRT1-transgenic mice. B16F10 mouse melanoma grew more quickly in SIRT1-transgenic mice than in wild-type mice, whereas SIRT1-overexpressing one grew slowly in both mice. Of human tumors, SIRT1 expression in stromal fibroblasts was found to correlate with poor prognosis in ovarian cancer. B16F10 and human ovarian cancer (SKOV3 and SNU840) cells were more proliferative in co-culture with SIRT1-overexpressiong fibroblasts. In contrast, SIRT1 within cancer cells has a negative effect on cell proliferation. In conditioned media from SIRT1-overexpressing fibroblasts, matrix metalloproteinase-3 (MMP3) was identified in cytokine arrays to be secreted from fibroblasts SIRT1-dependently. Fibroblastderived MMP3 stimulated cancer cell proliferation, and such a role of MMP3 was also demonstrated in cancer/fibroblast co-grafts. In conclusion, SIRT1 plays differential roles in cancer and stromal cells. SIRT1 in stromal cells promotes cancer growth by producing MMP3, whereas SIRT1 in cancer cells inhibits growth via an intracellular event. The present study provides a basis for setting new anticancer strategies targeting SIRT1.

Original languageEnglish
Pages (from-to)23975-23987
Number of pages13
JournalOncotarget
Volume7
Issue number17
DOIs
StatePublished - 26 Apr 2016

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Stromal Cells
Matrix Metalloproteinase 3
Fibroblasts
Neoplasms
Ovarian Neoplasms
Transgenic Mice
Cell Proliferation
Conditioned Culture Medium
Growth
Coculture Techniques
Melanoma
Cytokines
Transplants

Keywords

  • MMP3
  • SIRT1
  • Stroma
  • Tumor

Cite this

Shin, Dong Hoon ; Choi, Yong Joon ; Jin, Peng ; Yoon, Haejin ; Chun, Yang Suk ; Shin, Hyunwoo ; Kim, Ja Eun ; Park, Jong-Wan. / Distinct effects of SIRT1 in cancer and stromal cells on tumor promotion. In: Oncotarget. 2016 ; Vol. 7, No. 17. pp. 23975-23987.
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Distinct effects of SIRT1 in cancer and stromal cells on tumor promotion. / Shin, Dong Hoon; Choi, Yong Joon; Jin, Peng; Yoon, Haejin; Chun, Yang Suk; Shin, Hyunwoo; Kim, Ja Eun; Park, Jong-Wan.

In: Oncotarget, Vol. 7, No. 17, 26.04.2016, p. 23975-23987.

Research output: Contribution to journalArticleResearchpeer-review

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