- 期刊
- OpenAccess
The Unfolded Protein Response (UPR): A New Paradigm in Cancer Research
內質網蛋白不良摺疊效應：癌症研究的新觀念
摘要
本短篇綜說之目的是介紹一個新進的癌症研究新觀念，有關內質網不良蛋白摺疊效應，提供醫師們參考。首先，在缺氧的情況下，腫瘤細胞的一種重要的生理表徵是造成內質網壓力，在這種壓力下，腫瘤細胞會啟動蛋白不良摺疊效應，以求生存的機制。其中最顯著的生存保衛機制是轉錄誘發內質網相關保護蛋白，例如所謂的葡萄糖調控蛋白－78(GRP-78)。此種蛋白的表現，可以增進癌細胞對各類抗癌藥物的耐受性。本文將針對GRP-78與癌症的發生過程以及抗藥性所扮演之角色，以及其可能之機制簡單敘述，同時，GRP-78在臨床上的應用將以最新的研究實例加以說明，俾供參考。
並列摘要
This brief review is intended for the physicians to abreast the concept of this new emerging paradigm which has a trememdous impact in the field of cancer research. Hypoxia is physiologically important endoplasmic reticulum (ER) stress that is present in all solid tumors. Tumor cells respond to hypoxia and ER stress through the activation of the UPR. The UPR is an adaptive response to increase cell survival during ER stress. A prominent UPR protective response is the transcriptional activation of the ER stress chaperone glucose regulated protein 78 (GRP78) which is known to confer resistance to a variety of cancer therapy in both proliferating and dormant cancer cell in culture. In this review, the role of GRP78 in cancer progression and drug resistance will be briefly summarized. The possible underlying mechanisms of these attributes of GRP78 will also be discussed. Finally, the clinical applications of this ER stress-associated GRP78 will be exemplified with some newly reported research data.