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...
| Autor: | |
|---|---|
| Tipo de documento: | Tesis doctoral |
| Estado: | Published version |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/586316 |
| Acceso en línea: | http://hdl.handle.net/10803/586316 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | RANK RANKL Mammary gland Breast cancer Stem cell Metastasis Glándula mamaria Cancer de mama Célula progenitora 616 |
| _version_ | 1878731424796770304 |
|---|---|
| author | Pellegrini, Pasquale |
| author_browse | Pellegrini, Pasquale |
| author_facet | Pellegrini, Pasquale |
| author_role | author |
| collection | TDR. Tesis Doctorales en Red |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | doctoralThesis |
| id | ES_2f542e9780717d5ce2cf7d700de4e83e |
| institution | CBUC, CESCA |
| instname_str | CBUC, CESCA |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:www.tdx.cat:10803/586316 |
| publishDate | 2014 |
| publishDateSort | 2014 |
| publisher | Universitat Pompeu Fabra |
| publisherStr | Universitat Pompeu Fabra |
| reponame_str | TDR. Tesis Doctorales en Red |
| spelling | RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis Pellegrini, Pasquale RANK RANKL Mammary gland Breast cancer Stem cell Metastasis Glándula mamaria Cancer de mama Célula progenitora 616 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. RESUMEN La vía de RANK es esencial para el desarollo de la glándula mamaria y la tumorigénesis inducida por progesterona. Demostramos que RANK controla la especificación de linajes mamarios, y que un aumento de señalización a través de RANK induce una acumulación de células madre y progenitoras de mama con la consiguiente formación espontánea de tumores. RANK bloquea la diferenciación alveolar a través de la disminución de progenitoras alveolares CD61+ y la regulación de la via Elf-5/STAT5. Utilizando estrategias genéticas y farmacológicas demostramos que RANK promueve la formación, progresión tumoral y la metástasis de modelos de tumorigenesis espontánea de mama, y expande las poblaciones de células iniciadoras de tumores y células iniciadoras de metastasis. La vía de RANK media además la interacción entre las células tumorales y su entorno, modulando la respuesta inmune tumoral. El aumento en la expresión de RANK se correlaciona con la agresividad de tumores humanos y la metástasis. Estos resultados sugieren que la vía de RANK puede ser una nueva diana terapéutica en cáncer de mama. Programa de doctorat en Biomedicina Universitat Pompeu Fabra http://hdl.handle.net/10803/586316 |
| spellingShingle | RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis Pellegrini, Pasquale RANK RANKL Mammary gland Breast cancer Stem cell Metastasis Glándula mamaria Cancer de mama Célula progenitora 616 |
| status_str | publishedVersion |
| title | RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis |
| title_full | RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis |
| title_fullStr | RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis |
| title_full_unstemmed | RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis |
| title_short | RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis |
| title_sort | RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis |
| topic | RANK RANKL Mammary gland Breast cancer Stem cell Metastasis Glándula mamaria Cancer de mama Célula progenitora 616 |
| topic_facet | RANK RANKL Mammary gland Breast cancer Stem cell Metastasis Glándula mamaria Cancer de mama Célula progenitora 616 |
| url | http://hdl.handle.net/10803/586316 |