Related Experiment Video
Updated: Aug 11, 2026

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional (3D) Model
Published on: June 11, 2014
The estrogen-integrin αvβ3 crosstalk in breast cancer: Modulating PD-L1 and immune evasion
Dana R Crawford1, Yung-Ning Yang2, Feng-Cheng Liu3
1Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
Abstract:
The mechanisms governing PD-L1 expression in breast cancer are highly complex and context-dependent. This article proposes a novel "dual-track" regulatory model to resolve the conflicting roles of estrogen in tumor immunity. Genomic signaling through ER-α suppresses PD-L1 transcription, explaining lower PD-L1 levels in ER-α-positive tumors. Conversely, non-genomic signaling mediated by cell-surface integrin αvβ3 drives PD-L1 presentation by triggering downstream PI3K/Akt and MAPK/ERK 1/2 pathways. We synthesize emerging data on how post-translational modulators (RNF31, p66Shc) and metabolic regulators (SIRT1-NAD+ axis) fine-tune PD-L1 stability. This interplay reveals a therapeutic vulnerability: antiestrogen treatments can paradoxically increase surface PD-L1 expression. In triple-negative breast cancer (TNBC), the absence of ER-α combined with active integrin αvβ3 signaling accelerates PD-L1-mediated immune evasion. This comprehensive framework uncovers novel molecular targets to improve combined endocrine and immunotherapeutic regimens for breast cancer patients.
Related Concept Videos
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions
Some...
Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
The Tumor Microenvironment
Cancer Cell Migration through Invadopodia