Cell Rep: identify the key mechanism of promoting cell carcinogenesis

February 17, 2020 / Biovalley bio on / -- when the mechanism that guides stem cells to transform into somatic cells is shut down normally, cells will turn cancerous, identifying the mechanism that hinders this process or hopefully helping scientists find new cancer research targets; recently, an international journal Cell reports In the previous research report, scientists from Purdue University and other institutions found the epigenetic process that can make the stem cell enhancer in an active, activated or inhibited state, especially the researchers identified a protein protein interaction, which may block the normal formation of the above state Photo source: according to humaira gowher, Oct4 protein interferes with a series of events, which will turn off the "stem cell characteristics" of cells when they differentiate, so that cells can no longer replicate Removing these interferences will block the continuous proliferation of cancer cells; cancer is often difficult to clear, because it will maintain stem cells Now scientists have known that only a part of cancer cells can differentiate finally under the treatment of retinoic acid, and researchers can use embryonic cancer cells as a model to study the characteristics of drug-resistant cancer cells Previously, researchers have found that as normal embryonic stem cells continue to differentiate, they will use epigenetic silencing enhancer control elements to inhibit stem cell specific genes (stemness) through DNA methylation Genes), a special enzyme called LSD1, can help DNA methylation; however, these stem cell specific genes will not be completely inhibited in some cancer cells, and they will undergo partial differentiation; Gower pointed out that if normal stem cells are differentiated , which silences the pluripotent gene enhancer, but these cells do not, they will let the enhancer partially open, the researchers pointed out that these cells are in some intermediate state, rather than the final differentiation state The researchers say the promoter enhancer is very easy to activate, leading to cell proliferation, which may be why cancer stem cells are resistant to differentiation therapy In some cancers, researchers found that enhancers may exist in a startup state, which may help cancer stem cells survive or proliferate, which is a survival mechanism of cancer cells The activity of LSD1 may be inhibited by stem cell transcription factor Oct4 in cells, said researcher Gower Because of the abnormal existence of Oct4, cells cannot differentiate completely If the interaction between oct4-lsd1 is inhibited, or the degradation of Oct4 is targeted, cell differentiation may be promoted, which may be a potential target for the development of new cancer therapy The next step is to further study the molecular mechanism of the interaction between oct4-lsd1 and identify other transcription factors that may inhibit the activity of LSD1 Original source: Lama alabidi, debapuriya Saha, Ming He, et al Oct4 mediated initiation of LSD1 activity promotions the active and primed state of pluripotency enhancers Cell reports (2019) doi: 10.1016/j.celrep.2019.11.040