Castro, Jessica, Tornillo, Giusy, Ceada, Gerardo, Ramos-Neble, Beatriz, Bravo, Marlon, Ribo', Marc, Vilanova, Maria, Smalley, Matthew ORCID: https://orcid.org/0000-0001-9540-1146 and Benito, Antoni 2021. A nuclear-directed ribonuclease variant targets cancer stem cells and inhibits migration and invasion of breast cancer cells. Cancers 13 (17) , 4350. 10.3390/cancers13174350 |
PDF
- Published Version
Available under License Creative Commons Attribution. Download (13MB) |
Abstract
Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs' development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expression.
Item Type: | Article |
---|---|
Date Type: | Publication |
Status: | Published |
Schools: | Biosciences European Cancer Stem Cell Research Institute (ECSCRI) |
Publisher: | MDPI |
ISSN: | 2072-6694 |
Date of First Compliant Deposit: | 19 October 2021 |
Date of Acceptance: | 24 August 2021 |
Last Modified: | 29 Jun 2023 08:34 |
URI: | https://orca.cardiff.ac.uk/id/eprint/144132 |
Citation Data
Cited 1 time in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
Edit Item |