Aberrant Expression of Plastin-3 Via Copy Number Gain Induces the Epithelial–Mesenchymal Transition in Circulating Colorectal Cancer Cells
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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.
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.
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.
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.
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- Aberrant Expression of Plastin-3 Via Copy Number Gain Induces the Epithelial–Mesenchymal Transition in Circulating Colorectal Cancer Cells
Annals of Surgical Oncology
Volume 21, Issue 11 , pp 3680-3690
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
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- Industry Sectors
- Keishi Sugimachi MD, PhD (1)
- Takehiko Yokobori MD, PhD (1) (2)
- Hisae Iinuma PhD (3)
- Masami Ueda MD (1)
- Hiroki Ueo MD (1)
- Yoshiaki Shinden MD (1)
- Hidetoshi Eguchi MD, PhD (1)
- Tomoya Sudo MD, PhD (1)
- Akira Suzuki MD, PhD (4)
- Yoshihiko Maehara MD, PhD (5)
- Masaki Mori MD, PhD (6)
- Koshi Mimori MD, PhD (1)
- Author Affiliations
- 1. Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan
- 2. Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan
- 3. Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
- 4. Division of Cancer Genetics and Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
- 5. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- 6. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan