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

Year 2020, Volume: 7 Issue: 100. Yıl Özel Sayı, 329 - 343, 23.03.2020

Sinem Tunçer Ege Solel Sreeparna Banerjee

https://doi.org/10.35193/bseufbd.631769

Cited By: 2

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.

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

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