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It has been recognized clinically that cancer cells, especially the advanced and metastatic ones, possess characters reminiscent of those of normal stem cells.Many embryogenesis genes and pathways are reactivated during disease progression and contribute in tumor malignancy and prognosis.However, the underlying mechanisms of cancer cell dedifferentiation are still largely unclear.Compared with non-tumor tissues, we found the clinical stages of colorectal carcinoma correlate well with the reexpression of stem cell genes, with metastatic CRC being the most dedifferentiated one.Similar dedifferentiation scenario also occurs during the progression of endometrial endometrioid carcinoma, glioma and hepatocellular carcinoma.To explore genes responsible for dedifferentiation, metastasis genes were filtrated by our machine learning mining tool.Novel prognosis markers for colon cancers were found.Manipulating the expression of metastasis genes in colon cancer cells enhances cell motility and drug resistance and leads to metastatic, dedifferentiated transcriptome reprogramming.Cancer stem cell-like colonospheres could also be induced.Our results provide a quantitative measurement between stem cell traits and tumor histopathological stages and unmask the mechanisms.Filtrated dedifferentiating genes hold the potential of being novel therapeutic targets.