Kolon Kanseri Hücrelerinde Katlanmamış Protein Cevabının Aşırı Uyarılması VEGF İfadesini ve Salınımını Artırır

Abstract

Protein katlanması ve olgunlaşması Endoplazmik Retikulum (ER)’da gerçekleşir. ER fonksiyonundaki bozulmalar, yanlış katlanmış proteinlerin birikmesine neden olur ki bu durum “ER stresi” olarak bilinir. Katlanmamış Protein Yanıtı (Unfolded Protein Response-UPR), ER stresi durumunda hücresel homeostazın sağlanması için ER’de protein katlanmasının yeniden ve doğrulukla gerçekleştirilmesi amacı ile düzenlenmiş bir hücre sinyalizasyon programıdır. Bu çalışmada ER stresinin, kolon kanseri hücrelerinde VEGF (Vascular Endothelial Growth Factor) ifadesini ve VEGF’in hücre dışı salınımını arttırdığı gösterilmiştir. ER stresi modülatörleri kanser hücrelerinde ER stresine bağlı apoptozisi tetikleme potansiyelleri ile umut verici tedavi seçenekleri olarak sunulsa da, bu çalışma sonucu elde edilen veriler, ER stresini tetikleyici yaklaşımların, artmış otokrin/intrakrin VEGF sinyali ile tedaviye karşı dirence neden olabileceğini, hatta anjiyogenezi destekleyebileceğini öne sürmektedir.

Keywords

• Kolon kanseri,VEGF,VEGFR2,Katlanmamış Protein Yanıtı (UPR),ER stresi

Extensive Unfolded Protein Response Stimulation in Colon Cancer Cells Enhances VEGF Expression and Secretion

Abstract

Endoplasmic Reticulum (ER) is an important site for protein folding and maturation. Accumulation of unfolded or misfolded proteins in the ER leads to “ER stress”. The unfolded protein response (UPR) is a finely regulated cell-signaling program to re-establish ER folding capacity for building up cellular homeostasis. Although ER stress modulators have emerged as promising treatment options with their potential to trigger ER stress-mediated apoptosis in cancer cells, here we show that ER stress upregulates VEGF (Vascular Endothelial Growth Factor) expression and secretion in colon cancer cells, which may result in resistance against the treatment through enhanced autocrine/intracrine VEGF signaling and through supporting further angiogenesis.

Keywords

• Colorectal cancer,VEGF,VEGFR,Unfolded Protein Response (UPR),ER stress

Thanks

Sinem Tunçer is supported by TÜBİTAK, 2218-National Postdoctoral Research Fellowship Program. The financial support of Banerjee Lab. is gratefully acknowledged. The authors would like to thank Aydan Torun for the technical support.

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