一种新颖的计算预测生物学方法将Integrin β1区分为乳腺癌化疗抵抗的突出生物标志物。
A novel computational predictive biological approach distinguishes Integrin β1 as a salient biomarker for breast cancer chemoresistance.
发表日期：2023 Apr 10
作者：
Subhayan Das, Moumita Kundu, Atif Hassan, Aditya Parekh, Bikash Ch Jena, Swati Mundre, Indranil Banerjee, Rajesh Yetirajam, Chandan K Das, Anjan K Pradhan, Swadesh K Das, Luni Emdad, Pralay Mitra, Paul B Fisher, Mahitosh Mandal
来源：
Bba-Mol Basis Dis
摘要：
化疗耐药是乳腺癌治疗失败的主要原因之一，而蛋白质-蛋白质相互作用在乳腺癌进展的不同阶段中显著促进化疗耐药。为了寻找在乳腺癌化疗耐药出现期间出现的新生物标志物和相关的蛋白质-蛋白质相互作用，我们采用了计算预测生物学（CPB）方法。CPB识别出与不同与化疗耐药相关的乳腺癌蛋白质相连的蛋白质的粘附分子之间的关联。该方法鉴定了整合素β1（ITGB1）与化疗耐药和乳腺癌干细胞标志物的关联。ITGB1通过上调Erk磷酸化来激活FOCAL粘附激酶（FAK）途径，促进侵袭、迁移和化疗耐药。FAK还激活了Wnt / Sox2信号通路，增强了乳腺癌的自我更新。ITGB1通过激活FAK途径代表一种新的乳腺癌化疗耐药机制，可以通过干预ITGB1调节的信号通路开发新的治疗方法，阻止乳腺癌的进展。 版权所有 © 2023 Elsevier B.V.出版。
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.Copyright © 2023. Published by Elsevier B.V.