Catalytic domain of PRL-3 plays an essential role in tumor metastasis - Formation of PRL-3 tumors inside the blood vessels

被引:83
作者
Guo, K [1 ]
Li, J [1 ]
Tang, JP [1 ]
Koh, V [1 ]
Gan, BQ [1 ]
Zeng, Q [1 ]
机构
[1] Inst Mol & Cell Biol, Singapore 138673, Singapore
关键词
cancer therapy; cancer metastasis; colorectal cancer; protein-tyrosine phosphatase; angiogenesis;
D O I
10.4161/cbt.3.10.1111
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PRL-3, a protein tyrosine phosphatase, has attracted much attention as its transcript is consistently upregulated in the process of colorectal cancer metastases to secondary organs. We studied mice injected via the tail vein with CHO cells stably expressing EGFP-tagged PRL-3 or catalytically inactive mutant PRL-3 (C104S). Our data showed that the EGFP-PRL-3-expressing cells rapidly induce metastatic tumor formation in lung, while EGFP-PRL-3 (C104S)-expressing cells lose this metastastic activity. Furthermore, detailed microscopic examinations revealed that some EGF-PRL-3-, but not EGFP-PRL-3 (C104S)-, expressing cells form micro- and macro-metastatic solid tumors that sprout into blood vessels. Our studies provide clear evidence for a causative role of PRL-3 phosphatase activity in cancer metastasis and tumor-related angiogenesis events. The catalytic domain of PRL-3 could serve as an ideal therapeutic target for drug development to block the spread of colorectal cancer.
引用
收藏
页码:945 / 951
页数:7
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