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黏附连接异常蛋白能够通过赋予肝癌细胞干细胞样特性从而促进肿瘤的发生。

Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells.

机构信息

Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, South Korea.

出版信息

J Hepatol. 2011 Jan;54(1):122-31. doi: 10.1016/j.jhep.2010.06.026. Epub 2010 Aug 26.

Abstract

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is associated with a high potential for metastasis and disease recurrence, even after surgical resection. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence, and metastasis. Dysadherin is a prognostic indicator of metastasis and poor survival in many different cancer types. In this study, we investigated the possible link between dysadherin and CSC in HCC.

METHODS

We analyzed the functional implications of dysadherin on cancer stemness by modification of the dysadherin gene in HCC cell lines.

RESULTS

The transfection of dysadherin cDNA into the liver cancer cell line PLC/PRF/5 enhanced the properties of CSCs, including anti-apoptosis, their sphere-forming ability, side population phenotype, and tumor initiation ability in vivo. Furthermore, knockdown of dysadherin in the liver cancer cell line SK-Hep1 suppressed its stem cell-like properties.

CONCLUSIONS

These results show that dysadherin give rise to properties of CSC in HCC. Therefore, these findings suggest that dysadherin may be a potential molecular prognostic marker of HCC and may aid in the development of more effective therapies.

摘要

背景与目的

肝细胞癌(HCC)即使在手术后,也具有很高的转移和疾病复发的潜力。癌症干细胞(CSC)假说认为,CSC 是化疗耐药、复发和转移的原因。黏附素缺失与许多不同类型癌症的转移和不良预后相关。本研究旨在探讨 HCC 中黏附素缺失与 CSC 之间的可能联系。

方法

通过修饰 HCC 细胞系中的黏附素基因,分析黏附素缺失对癌症干性的功能影响。

结果

将黏附素 cDNA 转染入肝癌细胞系 PLC/PRF/5 中,增强了 CSC 的特性,包括抗凋亡、球体形成能力、侧群表型和体内肿瘤起始能力。此外,在肝癌细胞系 SK-Hep1 中敲低黏附素缺失抑制了其干细胞样特性。

结论

这些结果表明黏附素缺失赋予 HCC 中 CSC 的特性。因此,这些发现表明黏附素缺失可能是 HCC 的潜在分子预后标志物,并可能有助于开发更有效的治疗方法。

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