PTEN loss induces epithelial--mesenchymal transition in human colon cancer cells.
BACKGROUND
The epithelial-mesenchymal transition is a critical early event in the invasion and metastasis of many types of cancer, including colorectal cancer (CRC). Chronic inflammation is an inducer of several cancer types and inflammatory cytokines have been implicated in tumor invasion.


METHODS
Human colon cancer cell lines HCT116 and SW480 were transfected with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) siRNA or non-targeting control (NTC). Invasiveness was measured using a modified Boyden chamber assay and migration was assessed using a scratch assay.


RESULTS
PTEN knockdown increased the invasion and migration of CRC cells and the addition of medium containing tumor necrosis factor-alpha (TNF-alpha) further enhanced the migration and invasion. PTEN knockdown resulted in nuclear beta-catenin accumulation and increased expression of downstream proteins c-Myc and cyclin D1.


CONCLUSIONS
Our study supports the findings of clinical studies identifying an association of PTEN loss with late stage cancer. Cellular factors secreted from the surrounding tumor milieu likely act in concert with genetic changes in the tumor cells and contribute to enhanced tumor invasion.
Bowen
Kanika A
KA
Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093, USA.
Doan
Hung Q
HQ
Zhou
Binhua P
BP
Wang
Qingding
Q
Zhou
Yuning
Y
Rychahou
Piotr G
PG
Evers
B Mark
BM
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D006801:Humans; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014162:Transfection; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human