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|Title:||REGENERABLE ALTRUISM IN CLONAL CANCER CELLS||Authors:||MUHAMMAD SUFYAN BIN MASRONI||Keywords:||cancer, breast cancer, epigenetics, interactions, altruism, regeneration, social||Issue Date:||31-Jan-2018||Citation:||MUHAMMAD SUFYAN BIN MASRONI (2018-01-31). REGENERABLE ALTRUISM IN CLONAL CANCER CELLS. ScholarBank@NUS Repository.||Abstract:||Cancer is thought to involve predominantly selfish competition between cells. However, accumulating evidences indicate that cancer cells exhibit cooperative behaviours to promote tumour development. We studied a clonal breast cancer cell population with a heterogeneously-expressed endogenous microRNA, miR-125b, and report evidences of altruism. Increased population-wide tolerance to a taxane-based chemotherapeutic drug, docetaxel, is mediated by a minor fraction of cancer cells with high miR-125b expression. Cost-benefit analysis established the helping behaviour to be altruistic, as survival benefits rendered to miR-125b-low majority occurred at fitness cost to the miR-125b-high minority (the “altruists”). Interestingly, miR-125b-high altruists regenerated readily from a purified population of miR-125-low defectors, restoring the original population equilibrium. Targeting Krüpple-like Factor 2 (KLF2)-mediated histone acetylation disrupted this equilibrium, impeding the altruists’ regeneration and consequently blunting population-wide chemotolerance. Our findings indicate how epigenetics may underlie the dynamic plasticity and persistence of a small altruistic subpopulation to cope with unexpected environmental perturbation.||URI:||http://scholarbank.nus.edu.sg/handle/10635/145041|
|Appears in Collections:||Ph.D Theses (Open)|
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