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Abstract:
In malignant Breast tumours, cells experience hypoxic (low or no O 2 condition) and low-
nutrient conditions. However, some of these cancerous cells survive under a harsh hypoxic
environment, manage to escape chemotherapeutics, and later, once the therapy is withdrawn,
lead to cancer relapse. How these cancerous cells accomplish this by altering their
proliferative abilities while withstanding such harsh hypoxic growth conditions remains
poorly understood. Herein, by employing a systems biology approach, we demonstrate that
mammalian cell lines originating from breast tissues modulate their cell cycle dynamics by
resorting to endoreplication phenomenon to survive under various extents of hypoxic stress.
Our integrative approach predicts key regulators and interactions that can be experimentally
perturbed to eliminate therapeutically resistant cells under hypoxic conditions. These insights
will be crucial to formulate effective cancer therapeutic strategies. |