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ALDH1A3 通过影响 CXCR4 状态影响结肠癌的体外增殖和侵袭。

ALDH1A3 affects colon cancer in vitro proliferation and invasion depending on CXCR4 status.

机构信息

Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, #5 Dong Dan San Tiao, Beijing 100005, China.

Cell Resource Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, #5 Dong Dan San Tiao, Beijing 100005, China.

出版信息

Br J Cancer. 2018 Jan;118(2):224-232. doi: 10.1038/bjc.2017.363. Epub 2017 Dec 12.

DOI:10.1038/bjc.2017.363
PMID:29235568
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5785736/
Abstract

BACKGROUND

Aldehyde dehydrogenase (ALDH) has been widely used as a marker of cancer stem cells (CSCs). However, the ALDH family includes 19 members, and the most relevant isoforms and their biological functions in cancer biology are still controversial.

METHODS

We examined ALDH enzyme activity and the mRNA expression of 19 ALDH members in 58 human cell lines. The biological effect and mechanism of knocking down ALDH1A3 with siRNA and shRNA in cell lines were explored. Finally, the relationship between ALDH1A3 and CXCR4 was analysed in a large panel of cell lines.

RESULTS

ALDH1A3 is the key isoform that contributed to Aldefluor positivity in cell lines. Knocking down ALDH1A3 in different cancer cells conferred opposite phenotypes due to differential effects on CXCR4 expression. There was a significant negative correlation between ALDH1A3 and CXCR4 in 58 human cell lines.

CONCLUSIONS

ALDH1A3 was the main contributor to Aldefluor positivity in human cell lines, and its contrasting effects might arise from differences in CXCR4 expression.

摘要

背景

醛脱氢酶(ALDH)已被广泛用作癌症干细胞(CSC)的标志物。然而,ALDH 家族包括 19 个成员,其在癌症生物学中最相关的同工酶及其生物学功能仍存在争议。

方法

我们在 58 个人类细胞系中检测了 ALDH 酶活性和 19 个 ALDH 成员的 mRNA 表达。通过 siRNA 和 shRNA 敲低细胞系中 ALDH1A3 的生物学效应和机制进行了探索。最后,在大量细胞系中分析了 ALDH1A3 与 CXCR4 之间的关系。

结果

ALDH1A3 是导致细胞系中 Aldefluor 阳性的关键同工酶。由于对 CXCR4 表达的不同影响,在不同的癌细胞中敲低 ALDH1A3 赋予了相反的表型。在 58 个人类细胞系中,ALDH1A3 与 CXCR4 之间存在显著的负相关。

结论

ALDH1A3 是人类细胞系中 Aldefluor 阳性的主要贡献者,其相反的作用可能源于 CXCR4 表达的差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/f8cf061d2fba/bjc2017363f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/4eb0c0fc92a3/bjc2017363f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/e073a5f732ae/bjc2017363f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/abc2ebbf8413/bjc2017363f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/f10af0489f9c/bjc2017363f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/f8cf061d2fba/bjc2017363f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/4eb0c0fc92a3/bjc2017363f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/e073a5f732ae/bjc2017363f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/abc2ebbf8413/bjc2017363f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/f10af0489f9c/bjc2017363f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c24c/5785736/f8cf061d2fba/bjc2017363f5.jpg

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