2026-04-29T15:04:00Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/251742025-12-18T12:59:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Benítez, Sandra author Cordero, Alex author Santamaría, Patricia G author Redondo-Pedraza, Jaime author Rocha, Ana S author Collado-Solé, Alejandro author Jimenez, Maria author Sanz-Moreno, Adrian author Yoldi, Guillermo author Santos, Juliana C author De Benedictis, Ilaria author Gómez-Aleza, Clara author Da Silva-Álvarez, Sabela author Troulé, Kevin author Gómez-López, Gonzalo author Alcazar, Noelia author Palmero, Ignacio author Collado, Manuel author Serrano, Manuel author Gonzalez-Suarez, Eva author Benítez, Sandra author Cordero, Alex author Santamaría, Patricia G author Redondo-Pedraza, Jaime author Rocha, Ana S author Collado-Solé, Alejandro author Jimenez, Maria author Sanz-Moreno, Adrian author Yoldi, Guillermo author Santos, Juliana C author De Benedictis, Ilaria author Gómez-Aleza, Clara author Da Silva-Álvarez, Sabela author Troulé, Kevin author Gómez-López, Gonzalo author Alcazar, Noelia author Palmero, Ignacio author Collado, Manuel author Serrano, Manuel author Gonzalez-Suarez, Eva author 2021-06-21 Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models. Mechanistically, we have found that ectopic expression of Rank or exposure to Rankl induces senescence, even in the absence of other oncogenic mutations. Rank leads to DNA damage and senescence through p16/p19. Moreover, RANK-induced senescence is essential for Rank-driven stemness, and although initially translates into delayed tumor growth, eventually promotes tumor progression and metastasis. We uncover a dual role for Rank in the mammary epithelia: Rank induces senescence and stemness, delaying tumor initiation but increasing tumor aggressiveness. 34004159 https://hdl.handle.net/20.500.12105/25174 breast cancer mammary gland metastasis receptor activator of NFkB senescence senolytics stemness RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness.