RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis
RESUME RANK signaling is essential for mammary gland development and progesterone induced tumorigenesis. Here we show that RANK controls mammary stem cell fate; increased RANK signaling results in accumulation of stem and progenitor cells leading to spontaneous tumor formation. RANK signaling interf...
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| Format: | doctoral thesis |
| Status: | Published version |
| Publication Date: | 2014 |
| Country: | España |
| Institution: | CBUC, CESCA |
| Repository: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/586316 |
| Online Access: | http://hdl.handle.net/10803/586316 |
| Access Level: | Open access |
| Keyword: | RANK RANKL Mammary gland Breast cancer Stem cell Metastasis Glándula mamaria Cancer de mama Célula progenitora 616 |
| Summary: | RESUME RANK signaling is essential for mammary gland development and progesterone induced tumorigenesis. Here we show that RANK controls mammary stem cell fate; increased RANK signaling results in accumulation of stem and progenitor cells leading to spontaneous tumor formation. RANK signaling interferes with alveolar commitment through depletion of CD61+ alveolar progenitors and regulation of Elf-5/STAT5 pathway. Using pharmacological and genetic approaches we show that RANK signaling promotes tumor initiation, progression and metastasis in spontaneous breast cancer models and expands tumor initiating cells and metastasis initiating cells. RANK pathway mediates the crosstalk between tumor cells and their microenvironment modulating the tumor immune response. RANK expression correlates with aggressiveness and metastasis in human tumors. Altogether our data support that RANK signaling could be a novel therapeutic target in breast cancer. |
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