Authors
Qian Liang, Giada Zurlo, Junru Jin, Dengfeng Huang, Yudong Wei, Shuangjie Shen, Chengheng Liao, Tao Wang, Cheng Zhang, Jin Zhou, Hongyi Liu, Jun Fang, Haoyong Fu, Masashi Takeda, Xiang Li, Xiang David Li, Jian Zhou, Jinfan Wang, Tao Yue, James Brugarolas, Michael Buszczak, Qing Zhang
Published in
Molecular cell. Oct 12, 2026. Epub Oct 12, 2026.
Abstract
The mechanisms underlying renal cell carcinoma (RCC) progression remain incompletely understood. Here, we identify phytanoyl-CoA dioxygenase domain containing 1 (PHYHD1) as a tumor suppressor that regulates translational homeostasis and RCC progression. Progressive PHYHD1 loss promotes tumor advancement and predicts poor prognosis, as revealed by integrative deep learning analysis of pan-cancer datasets. Restoring PHYHD1 suppresses tumor growth in RCC cell and patient-derived xenograft (PDX) models independently of its dioxygenase activity. Mechanistically, PHYHD1 interacts with translation elongation factor eEF1A1, alters its association with ribosomes, and restrains protein translation. Ribosome profiling and RNA-seq identify ceramide transporter 1 (CERT1) as a key effector of the PHYHD1-eEF1A1 axis. PHYHD1 depletion enhances CERT1 translation, whereas targeting CERT1 impairs proliferation of PHYHD1-deficient cells. These findings define a PHYHD1-eEF1A1-CERT1 axis that controls translation during RCC progression and highlight CERT1 as a potential therapeutic target in PHYHD1-deficient tumors.
PMID:
42863464
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.
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