SLUG transcription factor: a pro-survival and prognostic factor in gastrointestinal stromal tumour.
BACKGROUND
The SLUG transcription factor has been linked with the KIT signalling pathway that is important for gastrointestinal stromal tumour (GIST) tumourigenesis. Its clinical significance in GIST is unknown.


METHODS
Influence of SLUG expression on cell proliferation and viability were investigated in GIST48 and GIST882 cell lines. The association between tumour SLUG expression in immunohistochemistry and recurrence-free survival (RFS) was studied in two clinical GIST series, one with 187 patients treated with surgery alone, and another one with 313 patients treated with surgery and adjuvant imatinib.


RESULTS
SLUG downregulation inhibited cell proliferation, induced cell death in both cell lines, and sensitised GIST882 cells to lower imatinib concentrations. SLUG was expressed in 125 (25.0%) of the 500 clinical GISTs evaluated, and expression was associated with several factors linked with unfavourable prognosis. SLUG expression was associated with unfavourable RFS both when patients were treated with surgery alone (HR=3.40, 95% CI=1.67-6.89, P=0.001) and when treated with surgery plus adjuvant imatinib (HR=1.83, 95% CI=1.29-2.60, P=0.001).


CONCLUSIONS
GIST patients with high tumour SLUG expression have unfavourable RFS. SLUG may mediate pro-survival signalling in GISTs.
Laboratory of Molecular Oncology, Translational Cancer Biology Research Program, Department of Oncology, University of Helsinki, P.O Box 63, FI-00014 University of Helsinki, Helsinki, Finland.
Olli-Pekka
OP
Pulkka
Department of Surgery, Sahlgrenska University Hospital, Gothenburg SE-41345, Sweden.
Bengt
B
Nilsson
Department of Pathology, HUSLab, University of Helsinki, Haartmaninkatu 3, FI-00029 HUS, Helsinki, Finland.
Maarit
M
Sarlomo-Rikala
Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Berlin-Buch, Schwanebecker Chaussee 50, Berlin 13125, Germany.
Peter
P
Reichardt
Department of Oncology, Skane University Hospital and Lund University, Lund SE-22185, Sweden.
Mikael
M
Eriksson
Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, P.O. Box 4953, Nydalen, Oslo N-0424, Norway.
Kirsten Sundby
KS
Hall
Gerhard-Domagk-Institute of Pathology, University Hospital Münster, Albert-Schweitzer-Campus 1, Building D17, Münster 48149, Germany.
Eva
E
Wardelmann
Helsinki Institute of Information Technology HIIT, Department of Computer Science, Aalto University, P.O. Box 15400, Espoo FI-00076, Finland.
Aki
A
Vehtari
Laboratory of Molecular Oncology, Translational Cancer Biology Research Program, Department of Oncology, University of Helsinki, P.O Box 63, FI-00014 University of Helsinki, Helsinki, Finland.|Department of Oncology, Helsinki University Hospital and University of Helsinki, P.O. Box 180, Helsinki FI-00290, Finland.
Heikki
H
Joensuu
Laboratory of Molecular Oncology, Translational Cancer Biology Research Program, Department of Oncology, University of Helsinki, P.O Box 63, FI-00014 University of Helsinki, Helsinki, Finland.
Harri
H
Sihto
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D000068877:Imatinib Mesylate