Researchers engineer a switch to tame aggressive cancers
Quoting from the ScienceDaily article: "Certain proteins, such as E-cadherin, are important for the maintenance of normal tissue structure. When tumors become more aggressive, they often lose E-cadherin, resulting in dramatic changes to their structure, function and ability to spread. But when cancer cells are forced to express E-cadherin, research suggests they behave less aggressively and revert back to normal." And, "'Although genomics technology has revealed many new proteins that could force cancers to 'switch' back to their less aggressive state, these new targets have not yet been validated in preclinical models like mice because it is difficult to determine the molecular effects on each individual cancer cell, Dr. Lewis says.'"
Cadherin and catenin mechanisms have been at the top of my list of possible candidates for the Cell Recognition Factor whose malfunction or disassociation and downstream malfunction of corrective mechanisms results in cancer. My hope continues to be that simply reconnecting cells with functioning adhesion molecules like cadherin might be sufficient; but I remain skeptical that the cancer cell would remain normal. The reason I say this is because I do not know the exact association between cadherin expression and genomic expression. The phenotype that you end up with and the epigenetic factors that enter the equation for a normal fully differentiated cell are unknown. Does cadherin determine the state of the DNA or does the state of the DNA determine the cadherin expression. If the former, then we are in good shape. The study shows that cadherin does influence phenotype but was it tissue-specific? Here, cadherin was introduced into a population of cancer cells and we can surmise that it bonded with catenin and vinculin and stabilized the cell, but was every essential element in place? Would the catenin undergo degradation because the cell had been in that mode? Nevertheless, this study is very promising.
Please see the Wikipedia article that beautifully shows the relationship between E-Cadherin and actin filaments via vinculin and catenin. The vinculin reminds me of a staple holding actin fibers against the cell membrane by adhering to E-cadherin sites. Breaking E-cadherin would release the vinculin which in turn would release the actin fibers. I believe that actin may play a role in freezing the nucleus' DNA expression or replication but I haven't heard of any work supporting this conjecture.
Additional support for the theory came when it was shown that some cancer cells express a protein-cleaving enzyme (hepsin) that breaks down cell-to-cell adhesion to facilitate metastasis. Why would a cancer cell produce such a substance? A cancer cell is known to be very much like an embryonic cell (EC). It is my contention that EC's need to keep the fluidity of their population. Adhesion would start the process of differentiation down an irreversible road. Any cells which are thus out of sync would need to have their CRF's cleaved in order to get back to pluripotency.
Quoting from the ScienceDaily article: "Certain proteins, such as E-cadherin, are important for the maintenance of normal tissue structure. When tumors become more aggressive, they often lose E-cadherin, resulting in dramatic changes to their structure, function and ability to spread. But when cancer cells are forced to express E-cadherin, research suggests they behave less aggressively and revert back to normal." And, "'Although genomics technology has revealed many new proteins that could force cancers to 'switch' back to their less aggressive state, these new targets have not yet been validated in preclinical models like mice because it is difficult to determine the molecular effects on each individual cancer cell, Dr. Lewis says.'"
Cadherin and catenin mechanisms have been at the top of my list of possible candidates for the Cell Recognition Factor whose malfunction or disassociation and downstream malfunction of corrective mechanisms results in cancer. My hope continues to be that simply reconnecting cells with functioning adhesion molecules like cadherin might be sufficient; but I remain skeptical that the cancer cell would remain normal. The reason I say this is because I do not know the exact association between cadherin expression and genomic expression. The phenotype that you end up with and the epigenetic factors that enter the equation for a normal fully differentiated cell are unknown. Does cadherin determine the state of the DNA or does the state of the DNA determine the cadherin expression. If the former, then we are in good shape. The study shows that cadherin does influence phenotype but was it tissue-specific? Here, cadherin was introduced into a population of cancer cells and we can surmise that it bonded with catenin and vinculin and stabilized the cell, but was every essential element in place? Would the catenin undergo degradation because the cell had been in that mode? Nevertheless, this study is very promising.
Please see the Wikipedia article that beautifully shows the relationship between E-Cadherin and actin filaments via vinculin and catenin. The vinculin reminds me of a staple holding actin fibers against the cell membrane by adhering to E-cadherin sites. Breaking E-cadherin would release the vinculin which in turn would release the actin fibers. I believe that actin may play a role in freezing the nucleus' DNA expression or replication but I haven't heard of any work supporting this conjecture.
Additional support for the theory came when it was shown that some cancer cells express a protein-cleaving enzyme (hepsin) that breaks down cell-to-cell adhesion to facilitate metastasis. Why would a cancer cell produce such a substance? A cancer cell is known to be very much like an embryonic cell (EC). It is my contention that EC's need to keep the fluidity of their population. Adhesion would start the process of differentiation down an irreversible road. Any cells which are thus out of sync would need to have their CRF's cleaved in order to get back to pluripotency.
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