Extensive Unfolded Protein Response Stimulation in Colon Cancer Cells Enhances VEGF Expression and Secretion
Kolon Kanseri Hücrelerinde Katlanmamış Protein Cevabının Aşırı Uyarılması VEGF İfadesini ve Salınımını Artırır

Sinem TUNÇER [1] , Ege SOLEL [2] , Sreeparna BANERJEE [3]


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.

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.

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Orcid: 0000-0002-8947-8646
Yazar: Sinem TUNÇER (Sorumlu Yazar)
Kurum: BILECIK SEYH EDEBALI UNIVERSITY
Ülke: Turkey


Orcid: 0000-0003-1120-0190
Yazar: Ege SOLEL
Kurum: University of Bergen
Ülke: Norway


Orcid: 0000-0003-4596-6768
Yazar: Sreeparna BANERJEE
Kurum: MIDDLE EAST TECHNICAL UNIVERSITY
Ülke: Turkey


Teşekkür 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.
Tarihler

Başvuru Tarihi : 10 Ekim 2019
Kabul Tarihi : 6 Mart 2020
Yayımlanma Tarihi : 23 Mart 2020

APA TUNÇER, S , SOLEL, E , BANERJEE, S . (2020). Extensive Unfolded Protein Response Stimulation in Colon Cancer Cells Enhances VEGF Expression and Secretion. Bilecik Şeyh Edebali Üniversitesi Fen Bilimleri Dergisi , 7 (100. Yıl Özel Sayı) , 329-343 . DOI: 10.35193/bseufbd.631769