Upregulation of CCT3 predicts poor prognosis and promotes cell proliferation via inhibition of ferroptosis and activation of AKT signaling in lung adenocarcinoma

• Published in: BMC cell biology 2022-06, Vol.23 (1), p.1-25, Article 25
• Main Authors: Wang, Kun, He, Jian, Tu, Changling, Xu, Hui, Zhang, Xugang, Lv, Yongchang, Song, Chao
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; AKT; AKT protein; Annexin V; Apoptosis; Autophagy; CCT3; Cell cycle; Cell death; Cell growth; Cell proliferation; Cell viability; Colonies; Cytotoxicity; Data analysis; Development and progression; Diagnosis; Experiments; Ferroptosis; Flow cytometry; Gene expression; Health aspects; LUAD; Lung cancer; Lung carcinoma; Medical prognosis; Oncogenes; Prognosis; Proteins; slc7a11; Squamous cell carcinoma
• ISSN: 2661-8850; 2661-8850; 1471-2121
• DOI: 10.1186/s12860-022-00424-7

Chaperonin containing TCP1 subunit 3 (CCT3) acts as an oncogene in cancers, whereas its role and underlying mechanisms in lung adenocarcinoma (LUAD) are poorly understood. This study investigated the clinical relevance and function of CCT3 in LUAD. We found that CCT3 was overexpressed in LUAD and LUSC tissues. Overexpression of CCT3 predicted the poor prognosis of LUAD patients. Loss-of-function and gain-of-function experiments demonstrated that CCT3 promoted the proliferation and colony formation of LUAD cells. In addition, CCT3 promoted cell cycle progression and suppressed slc7a11-mediated cell ferroptosis, but not apoptosis. We also found that CCT3 activated AKT. MK2206 significantly reduced the viability of CCT3 overexpressed LUAD cells, while had smaller inhibitory effect on the proliferation of control cells, suggesting that CCT3 dictates the sensitivity of LUAD cells to AKT inhibition. Our study demonstrates that CCT3 contributes to the proliferation and growth of LUAD cells through inhibition of ferroptosis and activation of AKT.