Paclitaxel Resistance Resulted in a Stem-Like State in Triple-Negative Breast Cancer: A Systems Biology Approach Publisher



Ghorbani M¹ ; Pourjafar F¹ ; Saffari M² ; Asgari Y¹ Show Affiliations
Source: Meta Gene Published:2020

Abstract

Therapy resistance is one of the most challenging problems in the way of treatment of cancer, especially in the case of triple-negative breast cancer which has a reputation of getting recur and resist. Therapy resistance is more likely explains by the Darwinian selection that is based on tumor heterogeneity and underlying mutations. Nevertheless, the concept of cancer cell plasticity becomes more attractive through a second hypothesis; non-Darwinian resistance which explains resistance could be also induced by other factors such as prolonged-stress and cancer cells could adopt an unrelated attractor-state to evade therapy. In this study, we have used a systems biology approach to explore MDA-MB-231 paclitaxel resistance based on the second hypothesis. According to the Gene Ontology (GO) findings and pathways analysis, resistant cells adopt some of the immune system-related processes. In addition, topological analyses showed IL17-RA to have a vital role in the network. Our findings also suggests that in the case of MDA-MB-231, paclitaxel resistance tries to push cells to a stem-like state, but not as typical breast cancer stem cells which are indicated by CD44(high)/CD24(low). The outputs could help to understand the underlying mechanism of the paclitaxel resistance breast cancer cell lines. © 2020 Elsevier B.V.