AKT1low quiescent cancer cells in ductal carcinoma in situ of the breast

Abstract

Ductal carcinoma in situ (DCIS) of the breast precedes the development of invasive breast cancer and reflects the genomic changes and protein expression profile of invasive disease. AKT1low cancer cells (QCC) are a rare, drug-tolerant, epigenetically plastic, and quiescent cancer cell subset that we previously identified at a frequency of 0.5–1% in primary breast tumors using the marker profile: AKTlow/H3K9me2low/HES1high. Here we used quantitative immunofluorescence microscopy with computational image analysis to show that AKT1low QCCs are present in DCIS from patients with and without co-existing invasive breast cancer. These data suggest that a drug-resistant, quiescent cancer cell state is present in premalignant breast lesions prior to the development of invasive disease. These findings warrant further study of whether AKT1low QCCs contribute to invasive tumor development and recurrence, similar to their role in more advanced malignancy.

Effect of AKT1 (p. E17K) Hotspot Mutation on Malignant Tumorigenesis and Prognosis

“…A state of drug-resistant, quiescent cancer cells (AKT1 low QCC) exists in premalignant breast lesions prior to the onset of aggressive disease. QCCs may be present in invasive lesions such as DCIS and are involved in the development and recurrence of aggressive tumors (Dey-Guha et al, 2011 ; Alves et al, 2018 ; Kabraji et al, 2019 ). QCCs are insensitive to radiotherapy and can evade organismal immune clearance, and upon activation can re-enter the cell cycle and replicate, ultimately leading to disease recurrence, complicating diagnosis and treatment of cancer patients and making it difficult to manage (Yeh and Ramaswamy, 2015 ).…”