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Title:
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Atypical cyclin P regulates cancer cell stemness through activation of the WNT pathway
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Author:
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Sánchez‑Botet, Abril; Quandt Herrera, Eva; Masip, Núria; Escribá, Rubén; Novellasdemunt, Laura; Gasa Colom, Laura; Li, Vivian S. W.; Raya, Ángel; Clotet Erra, Josep; Ribeiro, Mariana P. C.
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Notes:
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Purpose: Cancer stem cells represent a cancer cell subpopulation that has been found to be associated with metastasis and chemoresistance. Therefore, it is vital to identify mechanisms regulating cancer stemness. Previously, we have shown that the atypical cyclin P (CCNP), also known as CNTD2, is upregulated in lung and colorectal cancers and is associated with a worse clinical prognosis. Given that other cyclins have been implicated in pluripotency regulation, we hypothesized that CCNP may also play a role in cancer stemness. Methods: Cell line-derived spheroids, ex vivo intestinal organoid cultures and induced-pluripotent stem cells (iPSCs) were used to investigate the role of CCNP in stemness. The effects of CCNP on cancer cell stemness and the expression of pluripotency markers and ATP-binding cassette (ABC) transporters were evaluated using Western blotting and RT-qPCR assays. Cell viability was assessed using a MTT assay. The effects of CCNP on WNT targets were monitored by RNA-seq analysis. Data from publicly available web-based resources were also analyzed. Results: We found that CCNP increases spheroid formation in breast, lung and colorectal cancers, and upregulates the expression of stemness (CD44, CD133) and pluripotency (SOX2, OCT4, NANOG) markers. In addition, we found that CCNP promotes resistance to anticancer drugs and induces the expression of multidrug resistance ABC transporters. Our RNA-seq data indicate that CCNP activates the WNT pathway, and that inhibition of this pathway abrogates the increase in spheroid formation promoted by CCNP. Finally, we found that CCNP knockout decreases OCT4 expression in iPSCs, further supporting the notion that CCNP is involved in stemness regulation. Conclusion: Our results reveal CCNP as a novel player in stemness and as a potential therapeutic target in cancer. |
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Subject(s):
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-Cèl·lules mare del càncer (CSC)
-Càncer de colon
-Càncer de pulmó
-Ciclina P
-Células madre del cáncer (CSC)
-Cáncer de colon
-Cáncer de pulmón
-Ciclina P
-Cancer Stem Cells (CSC)
-Colon cancer
-Lung cancer
-Ciclina P
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Rights:
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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
http://creativecommons.org/licenses/by/4.0/
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Document type:
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Article
Article - Published version |
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Published by:
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Springer Nature
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