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《Chinese Science Bulletin》 2018-12
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Are stem cells at the heart of all cancers?

Xiaomei Zhu;Ping Ao;Shanghai Center for Quantitative Life Sciences and Physics Department, Shanghai University;Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University;  
For such a clearly posted question,the answer is negative.In fact,there was negative evidence when the question was raised in Science ten years ago.Why do Chinese and foreign researchers invest more effort in recent years to study the relationship between stem cells and cancer?And governments and private sectors are still increasing their financial support?First,are stem cells and cancers really related to phenomena and phenotypes?Stem cells are such important cell types in our body that they exist in a protected environment,and have the potential of self-renewal,high reproduction and differentiation.The cell renewal task in our body is done by them.The various processes of renewal are strictly regulated under normal condition.On the contrary,cancer cells are off normal regulation therefore can come from stem cells.During their pathological development and progression,their cellular and molecular factors involved in immunity and metabolism are different from those in normal processes.Cancer,in part,can be viewed as due to cells in an environment that is not suitable for their intended state.Since 1930’s,the answer to this type of expectation has been positively confirmed experimentally.The next question is,"are stem cells important for the development of cancer"?Due to the existence of stem cells in a protected environment,they are not sensitive to many common drug treatments and interventions.It immediately relates to an important phenomenon,at present not fully understood mystery—cancer’s drug resistance and recurrence.Chemotherapy is not effective to kill cancer associated stem cells.Meanwhile,two other major mysteries of cancer,tumor microenvironment and tumor metastasis,can also be partially explained by stem cells.Therefore,stem cells are important for cancer.At the core level of our problems,are stem cells really placed in the center of all cancers?Although stem cells can be used to understand the resistance of cancer to drugs,and can cause cancer themselves,they are not the whole of related phenomena.For example,cancer cells can be in a dormant state.Then,cancer cells are insensitive to many drugs.In addition to stem cells,other cell types can be transformed into cancer cells,too.From a completely different angle—the most popular theory at present—somatic mutation theory,the mutation in somatic cells can also lead to cancer.So,the experiments have already aptly proved that stem cells are not at the center of all cancers.The above negative answer is not satisfactory from the angle of clinical medicine;from the scientific point of view it does not provide a better understanding.Extensive nonlinear interactions between genes and proteins suggest a complex network at the molecular level.A large number of feedbacks make it not simple to distinguish between dynamical changes and dynamic behaviors.A systems biology theory for cancer is needed to integrate those perspectives.Hence,to address the question of stem cells vs.cancer is to ask for a completely new way to understand biology.The endogenous network theory proposed by Ao,Galas,Hood and Zhu in 2008 is such a best candidate.
【CateGory Index】: R730.2
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