herg1 gene and HERG1 protein are overexpressed in colorectal cancers and regulate cell invasion of tumor cells.
The acquisition of the capacity to invade surrounding tissues confers a more malignant phenotype to tumor cells and is necessary for the establishment of metastases. The understanding of the molecular mechanisms underlying cell invasion in human solid tumors such as colorectal cancers could provide not only more sensitive prognostic analyses but also novel molecular targets for cancer therapy. We report in this article that K(+) ion channels belonging to the HERG family are important determinants for the acquisition of an invasive phenotype in colorectal cancers. The herg1 gene and HERG1 protein are expressed in many colon cancer cell lines, and the activity of HERG channels modulates colon cancer cell invasiveness. Moreover, the amount of HERG1 protein expressed on the plasma membrane is directly related to the invasive phenotype of colon cancer cells. Finally, both the herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers, whereas no expression could be detected either in normal colonic mucosa or in adenomas.
Lastraioli
Elena
E
Department of Experimental Pathology and Oncology, University of Firenze, Firenze, Italy.
Guasti
Leonardo
L
Crociani
Olivia
O
Polvani
Simone
S
Hofmann
Giovanna
G
Witchel
Harry
H
Bencini
Lapo
L
Calistri
Massimo
M
Messerini
Luca
L
Scatizzi
Marco
M
Moretti
Renato
R
Wanke
Enzo
E
Olivotto
Massimo
M
Mugnai
Gabriele
G
Arcangeli
Annarosa
A
D027682:Cation Transport Proteins; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG