A Novel ER Stress Mediator TMTC3 Promotes Squamous Cell Carcinoma Progression by Activating GRP78/PERK Signaling Pathway.
A Novel ER Stress Mediator TMTC3 Promotes Squamous Cell Carcinoma Progression by Activating GRP78/PERK Signaling Pathway.
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新型 ER 应激介质 TMTC3 通过激活 GRP78/PERK 信号通路促进鳞状细胞癌进展
DOI：
10.7150/ijbs.72838
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发表时间：
2022
影响因子：
9.2
通讯作者：
Song, Yongmei
中科院分区：
文献类型：
--
作者：
Yuan, Hongyu;Zhao, Zitong;Guo, Zichan;Ma, Liying;Han, Jing;Song, Yongmei
During tumor progression, tumor cells are exposed to various stress conditions, which result in endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) to restore ER homeostasis. Accumulating evidence reported the orchestrating role of ER stress in epithelial-mesenchymal transition (EMT) progress, but the detailed mechanism was unclear. Here, we identified ectopic expression of TMTC3 in cells undergoing ER stress and verified the association with EMT markers through the cellular model of ER stress and database analysis. TMTC3 was abnormally highly expressed in squamous cell carcinomas (SCCs), and regulated by TP63, an SCCs-specific transcription factor. Biological function experiments indicated that TMTC3 promoted a malignant phenotype in vitro, and accelerated tumor growth and metastasis in vivo. RNA-seq analyses and further experiments revealed that TMTC3 promoted the expression of EMT markers via interleukin-like EMT inducer (ILEI, FAM3C). Further studies on the mechanism showed that TMTC3 disrupted the interaction between PERK and GRP78 to activate the PERK pathway and promote the nuclear translocation of ATF4, which increased the transcriptional activity of ILEI. These findings indicated that TMTC3 activates GRP78/PERK signaling pathway during ER stress-induced EMT, which might serve as a potential therapeutic target in SCCs.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
4.6
作者：
Kwak, Ah-Won;Choi, Joon-Seok;Shim, Jung-Hyun
通讯作者：
Shim, Jung-Hyun
DOI：
10.1073/pnas.1708319114
发表时间：
2017-10-17
影响因子：
11.1
作者：
Larsen, Ida Signe Bohse;Narimatsu, Yoshiki;Halim, Adnan
通讯作者：
Halim, Adnan
内质网应激在人类病理学中的作用。
DOI：
10.1146/annurev-pathol-012513-104649
发表时间：
2015
期刊：
Annual review of pathology
影响因子：
--
作者：
Oakes SA;Papa FR
通讯作者：
Papa FR
影响因子：
8.8
作者：
Campbell JD;Yau C;Bowlby R;Liu Y;Brennan K;Fan H;Taylor AM;Wang C;Walter V;Akbani R;Byers LA;Creighton CJ;Coarfa C;Shih J;Cherniack AD;Gevaert O;Prunello M;Shen H;Anur P;Chen J;Cheng H;Hayes DN;Bullman S;Pedamallu CS;Ojesina AI;Sadeghi S;Mungall KL;Robertson AG;Benz C;Schultz A;Kanchi RS;Gay CM;Hegde A;Diao L;Wang J;Ma W;Sumazin P;Chiu HS;Chen TW;Gunaratne P;Donehower L;Rader JS;Zuna R;Al-Ahmadie H;Lazar AJ;Flores ER;Tsai KY;Zhou JH;Rustgi AK;Drill E;Shen R;Wong CK;Cancer Genome Atlas Research Network;Stuart JM;Laird PW;Hoadley KA;Weinstein JN;Peto M;Pickering CR;Chen Z;Van Waes C
通讯作者：
Van Waes C