LIN28B promotes colon cancer progression and metastasis.
LIN28B promotes colon cancer progression and metastasis.
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LIN28B促进结肠癌的进展和转移。
DOI：
10.1158/0008-5472.can-10-4637
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发表时间：
2011-06-15
期刊：
影响因子：
11.2
通讯作者：
Rustgi AK
中科院分区：
文献类型：
--
作者：
King CE;Cuatrecasas M;Castells A;Sepulveda AR;Lee JS;Rustgi AK
LIN 28 B是LIN 28的同源物，当与体细胞成纤维细胞中的OCT 4、SOX 2和KLF 4一起表达时，LIN 28 B诱导多能性。LIN 28 B抑制let-7 microRNA的生物发生，并参与发育和肿瘤发生。最近，我们已经确定LIN 28 B过表达发生在结肠肿瘤中。我们对人结肠腺癌中Lin 28 b蛋白的表达进行了全面的分析。我们发现LIN 28 B过表达与患者生存率降低和肿瘤复发概率增加相关。为了阐明LIN 28 B的致瘤功能，我们在结肠癌细胞中组成型表达LIN 28 B并评估体内肿瘤形成。具有组成型Lin 28 b表达的肿瘤表现出结肠干细胞标志物LGR 5和PROM 1的表达增加、粘液分化和转移。总之，我们的发现指出LIN 28 B在促进结肠肿瘤发病机制，特别是转移中的功能。
LIN28B is a homolog of LIN28 which induces pluripotency when expressed in conjunction with OCT4, SOX2, and KLF4 in somatic fibroblasts. LIN28B represses biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Recently, we have determined that LIN28B overexpression occurs in colon tumors. We conducted a comprehensive analysis of Lin28b protein expression in human colon adenocarcinomas. We found that LIN28B overexpression correlates with reduced patient survival and increased probability of tumor recurrence. In order to elucidate tumorigenic functions of LIN28B, we constitutively expressed LIN28B in colon cancer cells and evaluated tumor formation in vivo. Tumors with constitutive Lin28b expression exhibit increased expression of colonic stem cell markers LGR5 and PROM1, mucinous differentiation, and metastasis. Together, our findings point to a function for LIN28B in promoting colon tumor pathogenesis, especially metastasis.