RANK signaling, a master regulator of mammary stemness and cancer : characterization of RANK and RANKL pathway stem cell fate, tumorigenesis and metastasis
Year: 2014
Type: dissertation
Abstract: 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.
Author: Pasquale Pellegrini
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G1980373154
OpenAlex ID: W2889135792