The diacylglycerol kinase α (DGKα)/Akt/NF-κB feedforward loop promotes esophageal squamous cell carcinoma (ESCC) progression via FAK-dependent and FAK-independent manner

被引：32

作者：

Chen, Jie ^{[1
]}

Zhang, Weimin ^{[1
]}

Wang, Yan ^{[1
]}

Zhao, Di ^{[1
]}

Wu, Mengjiao ^{[1
]}

Fan, Jiawen ^{[1
]}

Li, Jinting ^{[1
]}

Gong, Ying ^{[1
]}

Dan, Nana ^{[1
]}

Yang, Di ^{[1
]}

Liu, Rui ^{[1
]}

Zhan, Qimin ^{[1
,2
,3
,4
]}

机构：

[1] Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing,Lab Mol Oncol, Beijing 100142, Peoples R China

[2] Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst, Beijing 100021, Peoples R China

[3] Chinese Acad Med Sci, Canc Hosp, Beijing 100021, Peoples R China

[4] Peking Union Med Coll, Beijing 100021, Peoples R China

来源：

ONCOGENE | 2019年 / 38卷 / 14期

关键词：

FOCAL ADHESION KINASE; NF-KAPPA-B; EPIDERMAL-GROWTH-FACTOR; ACTIVATION; INFLAMMATION; AKT; PROLIFERATION; INHIBITION; MIGRATION; SUBUNIT;

D O I：

10.1038/s41388-018-0604-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Many reports have described DGK alpha as an oncogene, hence, we investigated its function and the underlying mechanisms in esophageal squamous cell carcinoma (ESCC) progression. This study demonstrated that DGK alpha was upregulated by inflammatory stimulants and formed feedforward loop with Akt/NF-kappa B signaling in ESCC cells. Mechanistically, DGK alpha-activated Akt/NF-kappa B signaling via stimulating PA production to reduce cAMP level and PTEN activity, and specifically, independently of its kinase function, through direct interaction with the FERM domain of FAK to relieve the auto-inhibitory effect of FERM domain on FAK. Overexpression of DGK alpha promoted cancer malignant progression both in vitro and in vivo, whereas depletion of DGK alpha suppressed these effects. Importantly, DGK alpha expression was tightly correlated with the malignancy of various inflammation-related squamous carcinomas and the oncogenic Akt/NF-kappa B activity. Therefore, DGK alpha is critically involved in inflammation-mediated ESCC progression, supporting DGK alpha as a potential target for ESCC therapy.

引用

页码：2533 / 2550

页数：18

共 41 条

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