School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, India.
Department of Computer Science & Engineering, Indian Institute of Technology Kharagpur, Kharagpur, India.
Biochim Biophys Acta Mol Basis Dis. 2023 Aug;1869(6):166702. doi: 10.1016/j.bbadis.2023.166702. Epub 2023 Apr 10.
Chemoresistance is a primary cause of breast cancer treatment failure, and protein-protein interactions significantly contribute to chemoresistance during different stages of breast cancer progression. In pursuit of novel biomarkers and relevant protein-protein interactions occurring during the emergence of breast cancer chemoresistance, we used a computational predictive biological (CPB) approach. CPB identified associations of adhesion molecules with proteins connected with different breast cancer proteins associated with chemoresistance. This approach identified an association of Integrin β1 (ITGB1) with chemoresistance and breast cancer stem cell markers. ITGB1 activated the Focal Adhesion Kinase (FAK) pathway promoting invasion, migration, and chemoresistance in breast cancer by upregulating Erk phosphorylation. FAK also activated Wnt/Sox2 signaling, which enhanced self-renewal in breast cancer. Activation of the FAK pathway by ITGB1 represents a novel mechanism linked to breast cancer chemoresistance, which may lead to novel therapies capable of blocking breast cancer progression by intervening in ITGB1-regulated signaling pathways.
化学耐药性是乳腺癌治疗失败的主要原因，蛋白质-蛋白质相互作用在乳腺癌进展的不同阶段对化学耐药性有重要贡献。为了寻找新的生物标志物和相关的蛋白质-蛋白质相互作用，以应对乳腺癌化学耐药性的出现，我们采用了计算预测生物学（CPB）方法。CPB 确定了黏附分子与与化学耐药性相关的不同乳腺癌蛋白相关的蛋白质之间的关联。该方法确定了整合素 β1（ITGB1）与化学耐药性和乳腺癌干细胞标志物的关联。ITGB1 通过上调 Erk 磷酸化激活粘着斑激酶（FAK）途径，促进乳腺癌的侵袭、迁移和化学耐药性。FAK 还激活了 Wnt/Sox2 信号通路，增强了乳腺癌的自我更新。ITGB1 激活 FAK 途径代表了一种与乳腺癌化学耐药性相关的新机制，这可能导致新的治疗方法能够通过干预 ITGB1 调节的信号通路来阻止乳腺癌的进展。
