Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling
- PMID: 21098263
- PMCID: PMC3003123
- DOI: 10.1073/pnas.1007863107
Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling
Abstract
Many tumors contain heterogeneous populations of cells, only some of which exhibit increased tumorigenicity and resistance to anticancer therapies. Evidence suggests that these aggressive cancer cells, often termed "cancer stem cells" or "cancer stem-like cells" (CSCs), rely upon developmental signaling pathways that are important for survival and expansion of normal stem cells. Here we report that, in analogy to embryonic mammary epithelial biology, estrogen signaling expands the pool of functional breast CSCs through a paracrine FGF/FGFR/Tbx3 signaling pathway. Estrogen or FGF9 pretreatment induced CSC properties of breast cancer cell lines and freshly isolated breast cancer cells, whereas cotreatment of cells with tamoxifen or a small molecule inhibitor of FGFR signaling was sufficient to prevent the estrogen-induced expansion of CSCs. Furthermore, reduction of FGFR or Tbx3 gene expression was able to abrogate tumorsphere formation, whereas ectopic Tbx3 expression increased tumor seeding potential by 100-fold. These findings demonstrate that breast CSCs are stimulated by estrogen through a signaling pathway that similarly controls normal mammary epithelial stem cell biology.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Similar articles
-
Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer-associated fibroblasts.J Pathol. 2019 Oct;249(2):193-205. doi: 10.1002/path.5290. Epub 2019 Jun 24. J Pathol. 2019. PMID: 31090071
-
Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications.Curr Drug Targets. 2019;20(8):852-870. doi: 10.2174/1389450120666190112145409. Curr Drug Targets. 2019. PMID: 30648505 Review.
-
The special stemness functions of Tbx3 in stem cells and cancer development.Semin Cancer Biol. 2019 Aug;57:105-110. doi: 10.1016/j.semcancer.2018.09.010. Epub 2018 Sep 27. Semin Cancer Biol. 2019. PMID: 30268432 Review.
-
Interaction between the estrogen receptor and fibroblast growth factor receptor pathways in non-small cell lung cancer.Oncotarget. 2017 Apr 11;8(15):24063-24076. doi: 10.18632/oncotarget.16030. Oncotarget. 2017. PMID: 28445992 Free PMC article.
-
Both autocrine and paracrine effects of transfected acidic fibroblast growth factor are involved in the estrogen-independent and antiestrogen-resistant growth of MCF-7 breast cancer cells.Cancer Res. 1998 Jan 15;58(2):352-61. Cancer Res. 1998. PMID: 9443417
Cited by
-
Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis.Nat Commun. 2024 May 15;15(1):4108. doi: 10.1038/s41467-024-48173-9. Nat Commun. 2024. PMID: 38750011 Free PMC article.
-
Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer.Front Oncol. 2024 Apr 18;14:1381251. doi: 10.3389/fonc.2024.1381251. eCollection 2024. Front Oncol. 2024. PMID: 38699644 Free PMC article. Review.
-
CDK7 in breast cancer: mechanisms of action and therapeutic potential.Cell Commun Signal. 2024 Apr 11;22(1):226. doi: 10.1186/s12964-024-01577-y. Cell Commun Signal. 2024. PMID: 38605321 Free PMC article. Review.
-
The impact of poor metabolic health on aggressive breast cancer: adipose tissue and tumor metabolism.Front Endocrinol (Lausanne). 2023 Sep 20;14:1217875. doi: 10.3389/fendo.2023.1217875. eCollection 2023. Front Endocrinol (Lausanne). 2023. PMID: 37800138 Free PMC article. Review.
-
Reprogramming of glucose metabolism via PFKFB4 is critical in FGF16-driven invasion of breast cancer cells.Biosci Rep. 2023 Aug 31;43(8):BSR20230677. doi: 10.1042/BSR20230677. Biosci Rep. 2023. PMID: 37222403 Free PMC article.
References
-
- Clarke MF, et al. Cancer stem cells—Perspectives on current status and future directions: AACR Workshop on Cancer Stem Cells. Cancer Res. 2006;66:9339–9344. - PubMed
-
- Ponti D, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 2005;65:5506–5511. - PubMed
-
- Yu F, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007;131:1109–1123. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical