1. Academic Validation
  2. FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells

FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells

  • Cancers (Basel). 2024 Sep 26;16(19):3269. doi: 10.3390/cancers16193269.
Xinyue Zhao 1 Zhihui Han 1 Ruiying Liu 1 Zehao Li 1 Ling Mei 1 Yue Jin 1 2 3
Affiliations

Affiliations

  • 1 Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
  • 2 National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
  • 3 Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Jilin University, Changchun 130061, China.
Abstract

Epithelial-to-mesenchymal transition (EMT) affects the invasion and migration of Cancer cells. Here, we show that FBXO11 recognizes and promotes ubiquitin-mediated degradation of ZEB1. There is a strong association between FBXO11 and ZEB1 in non-small cell lung Cancer (NSLC) in a clinical database. FBXO11 interacts with ZEB1, a core inducer of EMT. FBXO11 leads to increased ubiquitination and proteasomal degradation of ZEB1. Depletion of endogenous FBXO11 causes ZEB1 protein accumulation and EMT in A549 and H1299 cells, while overexpression of FBXO11 reduces ZEB1 protein abundance and cellular invasiveness. Importantly, the depletion of ZEB1 suppresses the increased migration and invasion of A549 and H1299 cells promoted by the depletion of FBXO11. The same results are shown in xenograft tumors. High FBXO11 expression is associated with a favorable prognosis in NSLC. Collectively, our study demonstrates that FBXO11 modulates EMT by mediating the stability of ZEB1 in lung Cancer cells.

Keywords

EMT; FBXO11; ZEB1; invasion and metastasis; lung cancer.

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