Endoplasmic Reticulum Stress and Pancreatic Cancer

Endoplazmik retikulum (ER) stres, farklı uyaranlar sonucu gelişen önemli hücresel bir olaydır. ER strese farklı yanıt türleri vardır. Bunlardan biri evrimsel olarak korunmuş katlanmamış protein cevabıdır (UPR). UPR'nin moleküllerin sonraki aktivasyonu için üç sensörü vardır. Bu sensörler inozitol gerektiren enzim 1 (IRE1), aktive edici transkripsiyon faktörü 6 (ATF6) ve protein kinaz RNA (PKR)-benzeri ER kinaz (PERK). ER stresin olmadığı durumlarda bu sensörler inaktif durumda tutulurlar. Ancak ER stres durumunda aktif hale gelirler ve yolaktaki alt basamak hedeflerini indüklerler. ER stresin sonucunda hücre ya canlı kalabilir ya da ölebilir. Pek çok çalışmada ER stresin farklı tipte hastalıklarla; örneğin diyabet, Alzheimer hastalığı, prion hastalığı, kanser vb; bağlantılı olduğu gösterilmiştir. Bir kanser türü olarak pankreas kanserinin de ER stres ile ilişkili olduğu gösterilmiştir. Pankreas kanseri geç tanısı ile birlikte düşük tedavi edilebilme potansiyeline sahiptir. Pankreas kanserinin ER stres ile olan ilişkisi yeni bir tedavi yaklaşımı olarak görülmektedir. Bu derlemenin amacı ER stresin tetiklediği mekanizmalar üzerine ve patogenezinde etkili olduğu hastalıklardan biri olan pankreas kanseri ile olan ilişkisine genel bir bakış yapmaktır.

Endoplazmik Retikulum Stresi ve Pankreas Kanseri

Endoplasmic reticulum (ER) stress, which results from different stimuli, is an important cellular event. There are different types of response to ER stress. One of them is evolutionarily conserved unfolded protein response (UPR). UPR has three sensors for further activation of molecules. These sensors are inositol-requiring enzyme 1 (IRE1), activated transcription factor 6 (ATF6), and ER-resident protein kinase RNA (PKR)-like ER kinase (PERK). In the absence of ER stress, these sensors are maintained in an inactive state. However, under ER stress conditions, they became activated and induce the downstream targets. As a consequence of ER stress, the cell may stay alive or became dead. Several studies have shown that ER stress is associated with different types of diseases such as diabetes mellitus, Alzheimer's disease, prion disease, and cancer. As a cancer type, it has been shown that pancreatic cancer is also associated with ER stress. Pancreatic cancer has a low cure potential with its late diagnosis. Its association with ER stress is seen as a new therapeutic approach. The aim of this is review is to provide an overview of the mechanisms of ER stress and its relationship with pancreatic cancer, one of the diseases in which ER stress affects pathogenesis.

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