A novel computational predictive biological approach distinguishes Integrin β1 as a salient biomarker for breast cancer chemoresistance

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

doi:10.1016/j.bbadis.2023.166702

A novel computational predictive biological approach distinguishes Integrin β1 as a salient biomarker for breast cancer chemoresistance

Biochim Biophys Acta Mol Basis Dis. 2023 Aug;1869(6):166702. doi: 10.1016/j.bbadis.2023.166702. Epub 2023 Apr 10.

Authors

Affiliations

¹ School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, India.
² Department of Computer Science & Engineering, Indian Institute of Technology Kharagpur, Kharagpur, India.
³ Anant National University, Ahmedabad, Gujarat, India.
⁴ School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, India; School of Pharmacy, Sister Nivedita University (Techno India Group), Kolkata, West Bengal, India.
⁵ Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
⁶ Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
⁷ School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur, India. Electronic address: mahitosh@smst.iitkgp.ac.in.

PMID: 37044238
DOI: 10.1016/j.bbadis.2023.166702

Abstract

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.

Keywords: Breast cancer; Cancer stem cell; Chemoresistance; Computational biology; FAK signaling; Integrin β1.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Biomarkers
Breast Neoplasms* / drug therapy
Cell Line, Tumor
Drug Resistance, Neoplasm
Female
Focal Adhesion Protein-Tyrosine Kinases / metabolism
Humans
Integrin beta1* / metabolism

Substances

Biomarkers
Focal Adhesion Protein-Tyrosine Kinases
Integrin beta1
Itgb1 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding