NANOG modulates stemness in human colorectal cancer.
NANOG modulates stemness in human colorectal cancer.
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DOI：
10.1038/onc.2012.461
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发表时间：
2013-09-12
期刊：
影响因子：
8
通讯作者：
Jessup, J. M.
中科院分区：
文献类型：
--
作者：
Zhang, J.;Espinoza, L. A.;Kinders, R. J.;Lawrence, S. M.;Pfister, T. D.;Zhou, M.;Veenstra, T. D.;Thorgeirsson, S. S.;Jessup, J. M.
NANOG是一种干细胞转录因子，对胚胎发育、正常成年细胞重编程和恶性转化和进展至关重要。几乎相同的逆转录基因NANOGP8在多种癌症中表达，但通常不在正常组织中表达，其功能也不明确。我们的假设是NANOGP8直接调节个体人类结直肠癌（CRC）细胞的干性。干细胞性在体外以无血清培养基中单个CRC细胞的球形性和侧群的大小来衡量，在体内以NOD/SCID小鼠的致瘤性和实验转移潜力来衡量。我们发现80%的临床肝转移表达NANOG， 75%的阳性转移含有NANOGP8转录物。6个结直肠癌系中，3 - 62%的单细胞在无血清培养基中形成球体。NANOGP8被翻译成蛋白质。在球体形成过程中，NANOG基因的相对表达量增加了8-122倍，比OCT4或SOX2转录本的表达量增加更多，而NANOGP8是更普遍的家族成员。shRNA对NANOG的抑制作用不仅可以抑制球性，还可以降低OCT4和SOX2的表达，降低侧群的大小和肿瘤的体内生长。抑制NANOG基因表达与抑制增殖和降低g2相关细胞周期蛋白的磷酸化有关。当NANOGP8基因表达受到抑制时，过表达NANOGP8可以恢复单细胞的球形性，并增加结直肠癌中的侧细胞数量。因此，NANOGP8可以代替NANOG直接促进结直肠癌的干性。
NANOG is a stem cell transcription factor that is essential for embryonic development, reprogramming normal adult cells and malignant transformation and progression. The nearly identical retrogene NANOGP8 is expressed in multiple cancers, but generally not in normal tissues and its function is not well defined. Our postulate is that NANOGP8 directly modulates the stemness of individual human colorectal carcinoma (CRC) cells. Stemness was measured in vitro as the spherogenicity of single CRC cells in serum free medium and the size of the side population and in vivo as tumorigenicity and experimental metastatic potential in NOD/SCID mice. We found that 80% of clinical liver metastases express a NANOG with 75% of the positive metastases containing NANOGP8 transcripts. 3 to 62% of single cells within 6 CRC lines form spheroids in serum free medium in suspension. NANOGP8 is translated into protein. The relative expression of a NANOG gene increased 8–122 fold during spheroid formation, more than the increase in OCT4 or SOX2 transcripts with NANOGP8 the more prevalent family member. shRNA to NANOG not only inhibits spherogenicity but also reduces expression of OCT4 and SOX2, the size of the side population and tumor growth in vivo. Inhibition of NANOG gene expression is associated with inhibition of proliferation and decreased phosphorylation of G2-related cell cycle proteins. Overexpression of NANOGP8 rescues single cell spherogenicity when NANOG gene expression is inhibited and increases the side population in CRC. Thus, NANOGP8 can substitute for NANOG in directly promoting stemness in CRC.
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影响因子：
3.7
作者：
Kong D;Banerjee S;Ahmad A;Li Y;Wang Z;Sethi S;Sarkar FH
通讯作者：
Sarkar FH
DOI：
10.1387/ijdb.103192sa
发表时间：
2010
期刊：
The International journal of developmental biology
影响因子：
--
作者：
Ambady S;Malcuit C;Kashpur O;Kole D;Holmes WF;Hedblom E;Page RL;Dominko T
通讯作者：
Dominko T
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
8
作者：
Jeter, C. R.;Liu, B.;Liu, X.;Chen, X.;Liu, C.;Calhoun-Davis, T.;Repass, J.;Zaehres, H.;Shen, J. J.;Tang, D. G.
通讯作者：
Tang, D. G.
影响因子：
14.9
作者：
Eberle I;Pless B;Braun M;Dingermann T;Marschalek R
通讯作者：
Marschalek R