KBTBD7 promotes non‐small cell lung carcinoma progression by enhancing ubiquitin‐dependent degradation of PTEN

Abstract

Abstract The Kelch repeat and BTB domain containing 7 (KBTBD7) was first cloned in 2010. Its function as a transcriptional activator and a substrate adaptor during the ubiquitination process was soon found. KBTBD7 was shown to be involved in excessive inflammation after myocardial infarction, brain development, and neurofibromin stability. However, studies on the role of KBTBD7 in solid tumors, especially lung cancer, are still lacking. Therefore, in this study, we investigate the role of KBTBD7 in non‐small cell lung cancer (NSCLC). Immunohistochemical staining of 102 paired NSCLC and peritumoral normal specimens indicated that KBTBD7 was highly expressed in NSCLC tissues and positively correlated with the histological type, P‐TNM stage, lymph node metastasis, and tumor size. KBTBD7 was also well‐expressed in NSCLC cell lines, and downregulation of KBTBD7 resulted in inhibition of NSCLC cell proliferation and invasion. Further investigation showed that KBTBD7 enhanced ubiquitin‐dependent degradation of PTEN, thus activating EGFR/PI3K/AKT signaling and promoting NSCLC cell proliferation and invasion by regulating CCNE1, CDK4, P27, ZEB‐1, Claudin‐1, ROCK1, MMP‐9, and E‐cadherin protein levels. Our results indicate that KBTBD7 may be a potential therapeutic target for the treatment of NSCLC.

Keywords

• epidermal growth factor
• invasion
• non‐small cell lung cancer
• proliferation
• PTEN
• the Kelch repeat and BTB domain containing 7