Endoplasmic Reticulum Stress and Tumor Microenvironment in Bladder Cancer: The Missing Link.
Endoplasmic Reticulum Stress and Tumor Microenvironment in Bladder Cancer: The Missing Link.
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DOI：
10.3389/fcell.2021.683940
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Nie Z;Chen M;Wen X;Gao Y;Huang D;Cao H;Peng Y;Guo N;Ni J;Zhang S
膀胱癌是泌尿系统常见的恶性肿瘤。尽管最近在局部或全身免疫治疗、化疗和放射治疗等治疗方面取得了进展，但高转移和复发率，特别是在肌肉浸润性膀胱癌(MIBC)中，导致了对更有针对性和个性化的治疗方法的评估。对膀胱癌发生机制的基本认识，以及针对膀胱癌相关过程和途径的治疗方法的发展，为膀胱癌的治疗提供了新的途径。越来越多的证据表明，肿瘤微环境(TME)可以由肿瘤细胞塑造，并相互作用于肿瘤细胞，重新编程和调节肿瘤的发展、转移和治疗反应。恶性TME由肿瘤的内在属性(如缺氧、氧化应激和营养缺乏)或外部应激源(如化疗和放射)引起，扰乱内质网(ER)蛋白质的正常合成和折叠过程，最终导致一种称为内质网应激(ER Stress)的有害情况。ERS是由未折叠蛋白反应(UPR)介导的一系列适应性变化，它交织成一个网络，最终介导细胞的增殖、凋亡和自噬，从而赋予肿瘤细胞更多的侵袭行为。此外，最近的研究表明，ERS还可以通过操纵TME来阻碍包括免疫治疗在内的抗癌治疗的效果。本文就膀胱癌、ERS和TME之间的关系进行讨论，总结目前克服治疗耐药的研究进展和面临的挑战，并探讨靶向ERS以改善膀胱癌治疗效果的概念。
Bladder cancer is a common malignant tumor of the urinary system. Despite recent advances in treatments such as local or systemic immunotherapy, chemotherapy, and radiotherapy, the high metastasis and recurrence rates, especially in muscle-invasive bladder cancer (MIBC), have led to the evaluation of more targeted and personalized approaches. A fundamental understanding of the tumorigenesis of bladder cancer along with the development of therapeutics to target processes and pathways implicated in bladder cancer has provided new avenues for the management of this disease. Accumulating evidence supports that the tumor microenvironment (TME) can be shaped by and reciprocally act on tumor cells, which reprograms and regulates tumor development, metastasis, and therapeutic responses. A hostile TME, caused by intrinsic tumor attributes (e.g., hypoxia, oxidative stress, and nutrient deprivation) or external stressors (e.g., chemotherapy and radiation), disrupts the normal synthesis and folding process of proteins in the endoplasmic reticulum (ER), culminating in a harmful situation called ER stress (ERS). ERS is a series of adaptive changes mediated by unfolded protein response (UPR), which is interwoven into a network that can ultimately mediate cell proliferation, apoptosis, and autophagy, thereby endowing tumor cells with more aggressive behaviors. Moreover, recent studies revealed that ERS could also impede the efficacy of anti-cancer treatment including immunotherapy by manipulating the TME. In this review, we discuss the relationship among bladder cancer, ERS, and TME; summarize the current research progress and challenges in overcoming therapeutic resistance; and explore the concept of targeting ERS to improve bladder cancer treatment outcomes.
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影响因子：
64.5
作者：
Cubillos-Ruiz JR;Silberman PC;Rutkowski MR;Chopra S;Perales-Puchalt A;Song M;Zhang S;Bettigole SE;Gupta D;Holcomb K;Ellenson LH;Caputo T;Lee AH;Conejo-Garcia JR;Glimcher LH
通讯作者：
Glimcher LH
DOI：
10.1073/pnas.0914072107
发表时间：
2010-08-31
影响因子：
11.1
作者：
Auf, Gregor;Jabouille, Arnaud;Moenner, Michel
通讯作者：
Moenner, Michel
影响因子：
--
作者：
Dadey DY;Kapoor V;Khudanyan A;Urano F;Kim AH;Thotala D;Hallahan DE
通讯作者：
Hallahan DE
影响因子：
3.7
作者：
Blaustein M;Pérez-Munizaga D;Sánchez MA;Urrutia C;Grande A;Risso G;Srebrow A;Alfaro J;Colman-Lerner A
通讯作者：
Colman-Lerner A
影响因子：
11.2
作者：
Clarke R;Cook KL;Hu R;Facey CO;Tavassoly I;Schwartz JL;Baumann WT;Tyson JJ;Xuan J;Wang Y;Wärri A;Shajahan AN
通讯作者：
Shajahan AN