RT Journal Article
T1 miR‐203 drives breast cancer cell differentiation
A1 Martínez Illescas, Nuria
A1 Leal, Silvia
A1 González, Patricia
A1 Graña Castro, Osvaldo
A1 Muñoz Oliveira, Juan José
A1 Cortés Peña, Alfonso
A1 Gómez Gil, María
A1 Vega, Zaira
A1 Neva, Verónica
A1 Romero, Andrea
A1 Quintela Fandino, Miguel
A1 Ciruelos Gil, Eva María
A1 Sanz, Consuelo
A1 Aragón, Sofía
A1 Sotolongo, Leisy
A1 Jiménez González, Sara
A1 Caleiras, Eduardo
A1 Mulero, Francisca
A1 Sánchez García, María Cristina
A1 Malumbres, Marcos
A1 Salazar Roa, María
AB A hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.
PB Springer
SN 1465-5411
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/95078
UL https://hdl.handle.net/20.500.14352/95078
LA eng
NO Martínez-Illescas, N.G., Leal, S., González, P. et al. miR-203 drives breast cancer cell differentiation. Breast Cancer Res 25, 91 (2023). https://doi.org/10.1186/s13058-023-01690-9
NO This work has been in part financed by benefactors, through the crowdfunding project “Match point against breast cancer” (PRECIPITA PR242, 2019; FECYT; Spanish Ministry of Science and Innovation, MICINN, led by MS‑R), and donations to Asociación Española contra el Cáncer (AECC). We are extremely thankful to all our donors. The work has been also funded by the Spanish Ministry of Science and Innovation and the Ministry of Economy and Competitiveness (supported with European Regional Development funds): PID2021‑128726 to MM, CNS2022‑135364 to MS‑R, PI20/00590 to CS, as well as by Comunidad de Madrid (Y2020/BIO‑6519 and S2022/BMD‑7437) to MM. MS‑R was supported by AECC (AIOA120833SALA and INVES18005SALA), a Juan de la Cierva incorporación and a Ramón y Cajal contract (RYC2020028929‑I, from the MICINN, FSE/ Agencia Estatal de Investigación). NGM‑I was supported by AECC (PRDMA19003GARC).
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Comunidad de Madrid
NO Ministerio de Economía, Comercio y Empresa (España)
NO Asociación Española contra el Cáncer
DS Docta Complutense
RD 9 abr 2025