Catalytic domain of PRL-3 plays an essential role in tumor metastasis: formation of PRL-3 tumors inside the blood vessels.
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.
Guo
Ke
K
Institute of Molecular and Cell Biology, Singapore.
Li
Jie
J
Tang
Jing Ping
JP
Koh
Vicki
V
Gan
Bin Qi
BQ
Zeng
Qi
Q
D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D016466:CHO Cells; D020134:Catalytic Domain; D006224:Cricetinae; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology*; D009389:Neovascularization, Pathologic; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D014183:Transplantation, Heterologous
D017874:Immediate-Early Proteins; C111534:Ptp4a3 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017027:Protein Tyrosine Phosphatases