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Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells.

Publication ,  Journal Article
Tesone, AJ; Rutkowski, MR; Brencicova, E; Svoronos, N; Perales-Puchalt, A; Stephen, TL; Allegrezza, MJ; Payne, KK; Nguyen, JM; Wickramasinghe, J ...
Published in: Cell Rep
February 23, 2016

Special AT-rich sequence-binding protein 1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating major histocompatibility complex class II (MHC II) expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46(+) inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

February 23, 2016

Volume

14

Issue

7

Start / End Page

1774 / 1786

Location

United States

Related Subject Headings

  • Transcription Factors
  • Signal Transduction
  • Receptor, Notch1
  • RNA, Small Interfering
  • Protein Binding
  • Promoter Regions, Genetic
  • Ovarian Neoplasms
  • Neoplasm Transplantation
  • Mice, Knockout
  • Mice
 

Citation

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Chicago
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Tesone, A. J., Rutkowski, M. R., Brencicova, E., Svoronos, N., Perales-Puchalt, A., Stephen, T. L., … Conejo-Garcia, J. R. (2016). Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells. Cell Rep, 14(7), 1774–1786. https://doi.org/10.1016/j.celrep.2016.01.056
Tesone, Amelia J., Melanie R. Rutkowski, Eva Brencicova, Nikolaos Svoronos, Alfredo Perales-Puchalt, Tom L. Stephen, Michael J. Allegrezza, et al. “Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells.Cell Rep 14, no. 7 (February 23, 2016): 1774–86. https://doi.org/10.1016/j.celrep.2016.01.056.
Tesone AJ, Rutkowski MR, Brencicova E, Svoronos N, Perales-Puchalt A, Stephen TL, et al. Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells. Cell Rep. 2016 Feb 23;14(7):1774–86.
Tesone, Amelia J., et al. “Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells.Cell Rep, vol. 14, no. 7, Feb. 2016, pp. 1774–86. Pubmed, doi:10.1016/j.celrep.2016.01.056.
Tesone AJ, Rutkowski MR, Brencicova E, Svoronos N, Perales-Puchalt A, Stephen TL, Allegrezza MJ, Payne KK, Nguyen JM, Wickramasinghe J, Tchou J, Borowsky ME, Rabinovich GA, Kossenkov AV, Conejo-Garcia JR. Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells. Cell Rep. 2016 Feb 23;14(7):1774–1786.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

February 23, 2016

Volume

14

Issue

7

Start / End Page

1774 / 1786

Location

United States

Related Subject Headings

  • Transcription Factors
  • Signal Transduction
  • Receptor, Notch1
  • RNA, Small Interfering
  • Protein Binding
  • Promoter Regions, Genetic
  • Ovarian Neoplasms
  • Neoplasm Transplantation
  • Mice, Knockout
  • Mice