“Destined to Die”, Neural Stem and Progenitor Cells as Possible Seedbeds for Cancer: A Hypothesis and Theoretical Model1

The ability to resist apoptotic and non-apoptotic cell death is considered to be a hallmark of cancer because all cancers share this characteristic [Hanahan and Weinberg, 2011]. How this particular hallmark facilitates the accumulation of oncogenic mutations without triggering apoptosis during the process of initiation and progression of the neoplasm and how it protects cancer cells from succumbing to anti-neoplastic therapies are well known [Wong 2011]. Many of the molecular mechanisms which contribute towards the empowerment of cancer cells with enhanced survival capabilities are well characterized [Allison et al 2012, Wong 2011]. Cancers develop as cancerous mutations accumulate. Some of these mutations contribute towards apoptotic resistance exhibited by different cancers. However acquirement of mutations indicates damages to the DNA. Such damages provoke apoptotic responses [Nowasheen et al 2012]. Therefore cells which serve as origins of neoplasms should already have heightened survival capabilities in order to survive the accumulation of mutations. The hypothesis and model presented in this article is an attempt to envisage a common mechanism through which certain cells may acquire increased apoptotic resistance and thus become ideally suited to serve as the seedbeds of cancers. The cell of origin of cancers has been a subject of intense speculation and debate with most of the attention being directed towards the multipotent stem cells and the oligopotent progenitor cells [Visvader and Lindeman 2012]. An oncogenic mutation might initiate a neoplastic process whose further development and subsequent progress depend upon the accumulation of further genetic and epigenetic aberrations [Hanahan and Wienberg 2011]. Cell proliferations and apoptosis are often closely related. Both during physiological and pathological conditions some of the cells in proliferating compartments undergo apoptosis [Al Enezi 2004].