Izgi Kenan, Canatan Halit, Iskender Banu
Department of Medical Biochemistry, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
Betul-Ziya Eren Genome and Stem Cell Centre, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
J Cancer Res Clin Oncol. 2017 Mar;143(3):371-383. doi: 10.1007/s00432-016-2258-5. Epub 2016 Sep 12.
The technology of reprogramming a terminally differentiated cell to an embryonic-like state uncovered the possibility of reprogramming a malignant cell back to a more manageable stem cell-like state. Since the current cancer models suffer from reflecting heterogeneous tumour structure and limited to express the late-stage markers, the induced pluripotent stem cell (iPSC) technology could provide an alternative model to recapitulate the early stages of cancer. Generation of iPSCs from cancer cells could offer a tool for understanding the mechanisms of tumour initiation-progression in vitro, a platform for studying tumour heterogeneity and origin of cancer stem cells and a source for cancer type-specific drug discovery studies.
In this review, we discussed the recent findings in reprogramming cancer cells with a special emphasis on similarities between cancer cells and pluripotent cells. We presented the basis of challenges in cancer cell reprogramming including the current problems in reprogramming, cancer-specific epigenetic state and chromosomal aberrations.
Cancer epigenetics represent the major hurdle before the prospective use of cancer iPSCs as a model system and for biomarker research. When the reprogramming process is optimised for cancer cell types, it might serve for two purposes: identification of the specific epigenetic state of cancer as well as reversion of the malignant phenotype to a potentially malignant but manageable state.
Reprogramming cancer cells would serve for our understanding of cancer-specific epigenome and elucidation of overlapping mechanisms shared by cancer-initiating cells and pluripotent cells.
将终末分化细胞重编程为胚胎样状态的技术揭示了将恶性细胞重编程回更易于管理的干细胞样状态的可能性。由于当前的癌症模型难以反映肿瘤的异质性结构且仅限于表达晚期标志物，诱导多能干细胞（iPSC）技术可为概括癌症早期阶段提供替代模型。从癌细胞生成诱导多能干细胞可为体外理解肿瘤起始-进展机制提供工具，为研究肿瘤异质性和癌症干细胞起源提供平台，并为癌症类型特异性药物发现研究提供来源。
在本综述中，我们讨论了癌细胞重编程的最新发现，特别强调了癌细胞与多能细胞之间的相似性。我们阐述了癌细胞重编程面临挑战的基础，包括重编程中的当前问题、癌症特异性表观遗传状态和染色体畸变。
癌症表观遗传学是诱导多能干细胞作为模型系统和生物标志物研究的前瞻性应用之前的主要障碍。当针对癌细胞类型优化重编程过程时，它可能有两个用途：识别癌症的特定表观遗传状态以及将恶性表型逆转到潜在恶性但可管理的状态。
重编程癌细胞将有助于我们理解癌症特异性表观基因组，并阐明癌症起始细胞和多能细胞共有的重叠机制。
