Details

Autor(en) / Beteiligte

• Lu, Jun
• Fu, Liang-Min
• Cao, Yun
• Fang, Yong
• Cao, Jia-Zheng
• Pan, Yi-Hui
• Cen, Jun-Jie
• Liang, Yan-Ping
• Chen, Zhen-Hua
• Wei, Jin-Huan
• Huang, Yong
• Mumin, Mukhtar Adan
• Xu, Quan-Hui
• Wang, Ying-Han
• Zhu, Jiang-Quan
• Liang, Hui
• Wang, Zhu
• Deng, Qiong
• Chen, Wei
• Jin, Xiao-Han
• Liu, Zhi-Ping
• Luo, Jun-Hang

Titel

LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway

Ist Teil von

• Oncogene, 2023-05, Vol.42 (19), p.1543-1557

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients' tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC.