Treatment-resistant breast cancer cells. Fluorescence light micrograph of breast cancer tissue, showing slowly proliferating cancer cells (red) that resist treatment. The red area is a cluster of slow-cycling (AKT-low/HES1-high) breast cancer cells within a human estrogen-receptor-positive (ER+) primary breast tumour. The cell nuclei are shown in blue, and rapidly cycling (AKT-high) cancer cells are shown in green. Cancer cells enter an AKT-low state in response to decreased interaction of cell surface beta-1 integrin with the extracellular matrix. AKT-low cancer cells within invasive breast cancer tumours persist after combination chemotherapy and contribute to tumour progression. AKT is protein kinase B. HES1 is a transcription factor.