Details

Autor(en) / Beteiligte

• Chen, Jie
• Zhang, Weimin
• Wang, Yan
• Zhao, Di
• Wu, Mengjiao
• Fan, Jiawen
• Li, Jinting
• Gong, Ying
• Dan, Nana
• Yang, Di
• Liu, Rui
• Zhan, Qimin

Titel

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

Ist Teil von

• Oncogene, 2019-04, Vol.38 (14), p.2533-2550

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Many reports have described DGKα as an oncogene, hence, we investigated its function and the underlying mechanisms in esophageal squamous cell carcinoma (ESCC) progression. This study demonstrated that DGKα was upregulated by inflammatory stimulants and formed feedforward loop with Akt/NF-κB signaling in ESCC cells. Mechanistically, DGKα-activated Akt/NF-κB 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 DGKα promoted cancer malignant progression both in vitro and in vivo, whereas depletion of DGKα suppressed these effects. Importantly, DGKα expression was tightly correlated with the malignancy of various inflammation-related squamous carcinomas and the oncogenic Akt/NF-κB activity. Therefore, DGKα is critically involved in inflammation-mediated ESCC progression, supporting DGKα as a potential target for ESCC therapy.