Multi-Stability and Consequent Phenotypic Plasticity in AMPK-Akt Double Negative Feedback Loop in Cancer Cells.

ABSTRACT: Adaptation and survival of cancer cells to various stress and growth factor conditions is crucial for successful metastasis. A double-negative feedback loop between two serine/threonine kinases AMPK (AMP-activated protein kinase) and Akt can regulate the adaptation of breast cancer cells to matrix-deprivation stress. This feedback loop can significantly generate two phenotypes or cell states: matrix detachment-triggered pAMPKhigh/ pAktlow state, and matrix (re)attachment-triggered pAkthigh/ pAMPKlow state. However, whether these two cell states can exhibit phenotypic plasticity and heterogeneity in a given cell population, i.e., whether they can co-exist and undergo spontaneous switching to generate the other subpopulation, remains unclear. Here, we develop a mechanism-based mathematical m

SUBMITTER: Chedere A 

PROVIDER: S-EPMC7865639 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature