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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 31, 2021 |
| Title |
STAT3 induces breast cancer growth and progression via IL-6, STC1 and MMP13 secretion by Cancer Associated Fibroblasts |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In the tumor microenvironment, Cancer Associated Fibroblasts (CAFs) become activated by cancer cells and increase their secretory activity to produce soluble factors that contribute to tumor cells proliferation, invasion and dissemination to distant organs. The pro-tumorigenic transcription factor STAT3 and its canonical inducer, the pro-inflammatory cytokine IL-6 act conjunctly in a positive feedback loop that maintains high levels of IL-6 secretion and STAT3 activation in both tumor and stromal cells. Here, we demonstrate that STAT3 is essential for the pro-tumorigenic functions of murine breast cancer CAFs both in vitro and in vivo, and identify a STAT3 signature significantly enriched for genes encoding for secreted proteins. Among those, IL-6, ANGPTL4, STC-1 and MMP13 were validated as STAT3-dependent mediators of CAF pro-tumorigenic functions by different approaches. CAFs activities were moreover impaired by IL-6 Receptor blocking antibodies and by MMP13 inhibition, supporting the feasibility of a therapeutic approach based on inhibiting STAT3-induced CAF-secreted proteins. The usefulness of such an approach is supported by the observation that an equivalent CAF-STAT3 signature in humans is expressed at high levels in breast cancer stromal cells and characterizes patients with a shorter disease specific survival, including those with basal-like disease.
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| Overall design |
In order to identify STAT3 transcriptional targets potentially mediating CAFs pro-oncogenic properties, we compared the mRNA expression profiles of primary CAFs, derived from NeuT transgenic mammary tumors, silenced or not for STAT3.
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| Contributor(s) |
Avalle L, Raggi L, Monteleone E, Savino A, Statello L, Camperi A, Aversano Stabile S, De Marzo N, Marino F, Guglielmi C, Zanini C, Forni M, Incarnato D, Oliviero S, Poli V |
| Citation(s) |
35042959 |
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| Submission date |
Jun 14, 2021 |
| Last update date |
Apr 01, 2022 |
| Contact name |
Aurora Savino |
| E-mail(s) |
[email protected]
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| Organization name |
Università di Torino
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| Street address |
via Nizza, 52
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| City |
Torino |
| State/province |
Piemonte |
| ZIP/Postal code |
10126 |
| Country |
Italy |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA737334 |
| SRA |
SRP323916 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE178081_Raw_gene_counts_matrix.txt.gz |
251.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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