Abstract
Early observations showed a lack of growth control and terminal differentiation with a lack of gap junctional intercellular communication (GJIC). Subsequent observations showed that epigenetic tumor promoters and activated oncogenes, which block gap junction function, provide insights into the multi-stage, multi-mechanism carcinogenic process. With the isolation of embryonic induced pluri-potent stem cells and organ-specific adult stem cells, gap junctions were linked to early development. While tumors and tumor cell lines are a heterogeneous mixture of “cancer stem cells” and “cancer non-stem cells”, the cancer stem cells seem to be of two types, namely, they express (a) no connexin genes or (b) connexin genes, but do not have functional GJIC. These observations suggest that these “cancer stem cells” originate from normal adult stem cells or from the de-differentiation or re-programming of somatic differentiated cells. This “Concept Paper” provides a hypothesis that “cancer stem cells” either originate from (a) organ-specific adult stem cells before the expression of the connexin genes or (b) organ-specific adult stem cells that just express gap junction genes but that the connexin proteins are rendered dysfunctional by activated oncogenes. Therefore, cancer prevention and therapeutic strategies must account for these two different types of “cancer stem cell”.
Highlights
Gap Junctional Intercellular Communication Differences between Normal and Cancer CellsOne of the universal characterizations of normal cells is that they are homeostatically regulated for growth control or are “contact inhibited” [3], can differentiate if they are stem cells, are able to apoptose, and are subject to senescence
In the cancer field, with all the subsequent findings related to the many unanswered properties of cancer cells and the carcinogenic process, such as oncogenes and tumor suppressor genes, one rarely sees any mention of this early observation
During the early evolution of multi-cellularity in vertebrate metazoans, the gap junction gene family appeared at the time when growth control, cellular differentiation and apoptosis cell functions appeared
Summary
Gap Junctional Intercellular Communication Differences between Normal and Cancer Cells. Cancers 2019, 11, 87 carcinogenic process to which their findings might be related They even raised this issue, “Do the induced changes in communication represent intermediate stages in the genesis of cancer, that is, intermediate stages in the transformation of normal into cancer cells? The finding they made did have strong implications that this might be a universal characterization of all cancer cells Even to this day, in the cancer field, with all the subsequent findings related to the many unanswered properties of cancer cells and the carcinogenic process, such as oncogenes and tumor suppressor genes, one rarely sees any mention of this early observation. The objective of this short “Concept paper” is to examine if all cancer cells have the same correlation with the gap junction or connexin genes and their functions
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