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12541_6516973_benitez_et_al_dev_cell_2021.pdf (4.22 MB)

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2021-01-01

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cc by-nc-nd (c) Benítez et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/177852

RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness

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Recurs relacionat

https://doi.org/10.1016/j.devcel.2021.04.022

Resum

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.

Matèries

Càncer de mama, Metàstasi, Cicle cel·lular

Matèries (anglès)

Breast cancer, Metastasis, Cell cycle

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Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
<b>Publicacions de projectes de recerca finançats per la UE</b>
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

BENÍTEZ, Sandra, CORDERO, Alex, SANTAMARÍA, Patricia g., REDONDO PEDRAZA, Jaime, ROCHA, Ana s., COLLADO-SOLÉ, Alejandro, JIMENEZ, Maria, SANZ MORENO, Adrian, YOLDI, Guillermo, SANTOS, Juliana c., BENEDICTIS, Ilaria de, GÓMEZ ALEZA, Clara, SILVA ÁLVAREZ, Sabela da, TROULÉ, Kevin, GÓMEZ LÓPEZ, Gonzalo, ALCAZAR, Noelia, PALMERO, Ignacio, COLLADO, Manuel, SERRANO MARUGÁN, Manuel, GONZÁLEZ SUÁREZ, Eva. RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness. _Developmental Cell_. 2021. Vol. 56. [consulta: 10 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/177852]

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