CSA Antisense Targeting Enhances Anticancer Drug Sensitivity in Breast Cancer Cells, including the Triple-Negative Subtype
Author(s)
Date Issued
2022
Type
article
Volume
14
Issue
7
Journal
Abstract
Breast cancer (BC), the most frequent malignancy in woman, shows a high rate of cancer recurrence and resistance to treatment, particularly in Triple-Negative Breast Cancer (TNBC) subtype. Starting from the observation that different subtypes of BC cells, including the TNBC one, display an increased expression of Cockayne Syndrome group A (CSA) protein, which is involved in multiple functions such as DNA repair, transcription and in conferring cell robustness when it is up-regulated, we demonstrated that CSA ablation by AntiSense Oligonucleotides (ASOs) drastically impairs tumorigenicity of BC cells by hampering their survival and proliferative capabilities without affecting normal breast cells. Suppression of CSA does result in lowering the IC50 value of Oxaliplatin and Paclitaxel, two commonly used chemotherapeutic agents in breast cancer treatment, allowing the use of a very low dose of chemotherapeutic that is non-toxic to the normal breast cell line. Finally, CSA ablation restores drug sensitivity in oxaliplatin-resistant cells. Based on these findings, we can conclude that CSA may be a very attractive target for the development of new specific anticancer therapies.
File(s)![Thumbnail Image]()
Name
cancers-14-01687-v2.pdf
Size
1.94 MB
Format
Adobe PDF
Checksum (MD5)
b944d60d45ea86c71d4c498c9c802082