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. 2017 Apr 25;116(9):1195-1202.
doi: 10.1038/bjc.2017.82. Epub 2017 Mar 23.

SLUG transcription factor: a pro-survival and prognostic factor in gastrointestinal stromal tumour

Olli-Pekka Pulkka  1 , Bengt Nilsson  2 , Maarit Sarlomo-Rikala  3 , Peter Reichardt  4 , Mikael Eriksson  5 , Kirsten Sundby Hall  6 , Eva Wardelmann  7 , Aki Vehtari  8 , Heikki Joensuu  1   9 , Harri Sihto  1
Affiliations

SLUG transcription factor: a pro-survival and prognostic factor in gastrointestinal stromal tumour

Olli-Pekka Pulkka et al. Br J Cancer. .

Abstract

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SLUG expression in GIST, and association with recurrence-free survival.An example of negative (A) and positive (B) expression of SLUG in GIST (magnification × 200). Association of tumour SLUG expression with recurrence-free survival in the western Sweden population-based series (C), and in the SSGXVIII/AIO series (D).
Figure 2
Figure 2
SLUG and KIT siRNA silencing in GIST cell lines.An example of SLUG, KIT and actin expression after siRNA transfection in the GIST882 (A) and the GIST48 (B) cell line. Cell proliferation decreased (C, D) and the rate of cell death (E, F) increased in the GIST882 cell line and in the GIST48 cell line after transfection with KIT or SLUG siRNA. An efficacy of imatinib in the GIST882 cell line was enhanced by the downregulation of SLUG expression (G). The simultaneous downregulation of SLUG expression and KIT inhibition sensitised GIST882 cells to lower imatinib concentration (H).
See this image and copyright information in PMC

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