9. Cell Proliferation from Regulated to Deregulated States Via Epigenomic Responses

It was established in the previous chapters that cells, under chronic conditions of hypoxia and/or ROS accumulation, must evolve for survival to overcome the pressure created by continuous glycolytic-metabolite accumulation plus possibly other pressures. This leads to continuous synthesis and export of hyaluronic acids in the early stage of a cancer development, as observed in many cancers. The fragments of the hyaluronic acid chains released into the pericellular space immediately become signals for inflammation, cell-cycle activation, cell proliferation, cell survival and angiogenesis, all designed for tissue repair except that no tissue is injured here. These molecules are continuously generated as long as the hypoxic or ROS conditions persist, hence providing driving signals for tissue repair on a continuous basis. In contrast, when a tissue is indeed injured, the hyaluronic acid fragments are released from the damaged underlying ECM rather than from the cells directly, hence the signaling will not continue indefinitely.