2. Academic Validation
  3. FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells

FAM129A promotes self-renewal and maintains invasive status via stabilizing the Notch intracellular domain in glioma stem cells

  • Neuro Oncol. 2023 Apr 21;noad079. doi: 10.1093/neuonc/noad079.
Guohao Liu 1,  Po Zhang 2,  Sui Chen 1,  Zirong Chen 1,  Yanmei Qiu 3,  Peng Peng 4,  Wenda Huang 1,  Fangling Cheng 5,  Yang Zhang 6,  Huan Li 6,  Qungen Xiao 1,  Feng Mao 1,  Baofeng Wang 1,  Xiaobing Jiang 2,  Feng Wan 7,  Dongsheng Guo 1,  Xingjiang Yu 6
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Neurosurgery, Xiangyang Central Hospital, Affiliated Hospital to Hubei University of Arts and Science, Xiangyang, China.
  • 5 Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 6 Department of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 7 Department of Neurosurgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
PMID: 37083136 DOI: 10.1093/neuonc/noad079
Abstract

Background: Glioma stem cells (GSCs) are a subpopulation of tumor cells with self-renewal and tumorigenic capabilities in glioblastomas (GBMs). Diffuse infiltration of GSCs facilitates tumor progression and frustrates efforts at effective treatment. Further compounding this situation is the currently limited understanding of what drives GSC invasion. Here we comprehensively evaluated the significance of a novel invasion-related protein, Family with Sequence Similarity 129 Member A (FAM129A), in infiltrative GSCs.

Methods: Western blotting, immunohistochemistry, and gene expression analysis were used to quantify FAM129A in glioma specimens and Cancer datasets. Overexpression and knockdown of FAM129A in glioma stem cells were used to investigate its effects on tumor growth and invasion. RNA-seq, qRT-PCR, western blotting, and co-precipitation assays were used to investigate FAM129A signaling mechanisms.

Results: FAM129A is preferentially expressed in invasive frontiers. Targeting FAM129A impairs GSC invasion and self-renewal. Mechanistically, FAM129A acted as a positive regulator of Notch signaling by binding with the Notch1 intracellular domain (NICD1) and preventing its degradation.

Conclusion: FAM129A and NICD1 provide a precise indicator for identifying tumor margins and aiding prognosis. Targeting them may provide a significantly therapeutic strategy for GSCs.

Keywords

FAM129A; NICD; Notch pathway; glioma stem cell; tumor invasion.

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