Understanding the Cancer Stem Cell Mechanistic in Model-Systems

Regenerative medicine is a relatively newly evolving branch in modern day medical innovations, which utilizes cell-based therapies that use healthy cells cultured in vitro/ lab to replace damaged cells/tissues in adult organisms, to treat disease or any accidental impairment. This, if achieved completely, could consequently hold the key for addressing and treating ailments, which currently have no promising cures; such as: Cancers, Neurological disorders, Alzheimer’s disease, spinal cord injury, cerebral palsy, brain stroke, muscular dystrophy, multiple sclerosis, diabetes, cardiovascular disorders, bone disorders, hematopoietic disorders, hepatic, renal and dermatological disorders. Earlier studies in stem cell biology have been focused mainly on the isolation and culture of tissue-specific stem cells from various sources and defining their unique properties. However, the challenge has now shifted towards understanding genetic programs controlling stem cell fate i.e. self-renewal and their multi-potential differentiation. Earlier studies have suggested a potential pathological role for Wingless (Wnt), Hedgehog (Hh), Notch (N) and BMP signaling pathways, which are all known to be well-conserved during evolution and have long been implicated in direct growth and patterning during embryonic development. Very recent data also indicates that these pathways are involved in post-embryonic regulation of stem cell number in epithelial derivatives such as skin and intestine, which undergo constant renewal since these cells have a relatively shorter life span[1]. The oncogenic inactivation of these pathways can occur at many levels. In particular, an aberrant inactivation of canonical Wnt signaling pathway is a major feature in human neoplasia. Current evidence indicates that a typical transformation process also exploits a unique physiological dependence of intestinal progenitor/stem cell on the Wnt cascade, thus suggesting, that the Wnt pathway could be a common and critical element in regulating stem cell renewal and/or maintenance in a variety of systems. Some of the common, conserved and important signaling pathways between invertebrates and vertebrates (like, Wnt, Notch, Hh) and the factors that are involved in such pathways would be the major targets for such an investigation, involving a pertinent genetic approach. The Wnt protein is a versatile protein that stars in multiple cell dramas, from embryonic development to cancer. Wnt, turns out to have yet another important role. It coaxes blood stem cells to divide briskly, lending hope that it may make it easier to experiment on stem cells and effectively apply them in therapy. An integral involvement of Wnt cascade in both cancer and stem cell maintenance and growth of epidermal, intestinal and haematopoetic systems may serve as a classic paradigm for understanding the dual nature of self-renewal signals. It would be indeed very interesting to further exploit wg/Wnt-stem cell connection or other signaling pathways, for pinpointing those handful yet critical set of “genetic factors” which might be critically required for the tinkering of stem cell status to transformed status in cancerous tissues or even the transformed status in an experimental model organism, like Drosophila (fruitfly). One of the prominent features of cancer cells is their unlimited cell division capacity, reminiscent of self-renewing proliferation characteristic of stem cell, which is indeed very striking. Notably, these “blank slates” i.e., stem cells also respond to a tuned feedback mechanism, that efficiently senses the number of mature cells and regulates the rate of division[7], whereas in cancer cells, this mechanism is abruptly interrupted. Their differences apart, this particular feature helps the stem cells to repair and regenerate the lost tissue/cells after trauma/damage in the body. One of the building blocks of this kind of therapy are these very “stem Understanding the Cancer Stem Cell Mechanistic in Model-Systems