Aberrant expression of plastin-3 via copy number gain induces the epithelial-mesenchymal transition in circulating colorectal cancer cells.
OBJECTIVE
Plastin-3 (PLS3) is a novel marker for circulating tumor cells (CTCs) in colorectal cancer (CRC). We sought to investigate the mechanisms mediating the aberrant expression of PLS3, the role of PLS3 in the epithelial-mesenchymal transition (EMT), and its association with the acquisition of invasive and metastatic abilities in human CRC.


METHODS
The expression levels of PLS3 messenger RNA in the tumor drainage venous blood (TDB) were examined in 177 CRC cases, and the associations between PLS3 expression and Xq23 copy numbers were analyzed in 132 CRC samples. We then established a stable PLS3-expressing CRC cell line and assessed the role of PLS3 in the EMT.


RESULTS
In clinical CRC cases, high expression of PLS3 in CTCs of TDB as well as peripheral blood was established as an independent prognostic factor of overall survival (p < 0.001), and the copy number gain of Xq23, which is the locus of the PLS3 gene, was significantly related to PLS3 overexpression. PLS3 induced the EMT via transforming growth factor (TGF)-β signaling and resulted in the acquisition of invasive ability in CRC cells.


CONCLUSIONS
The aberrant expression of PLS3 was associated with copy number gain in CTCs from primary tumors and was involved in the regulation of the EMT, contributing to a poor prognosis in CRC patients.
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Keishi
K
Sugimachi
Takehiko
T
Yokobori
Hisae
H
Iinuma
Masami
M
Ueda
Hiroki
H
Ueo
Yoshiaki
Y
Shinden
Hidetoshi
H
Eguchi
Tomoya
T
Sudo
Akira
A
Suzuki
Yoshihiko
Y
Maehara
Masaki
M
Mori
Koshi
K
Mimori
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D056915:DNA Copy Number Variations / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C026742:plastin