Related Experiment Video
Updated: May 24, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
METTL3 enhances esophageal squamous cell carcinoma progression by suppressing ferroptosis through the PBX3/CA9
Lingxia Yang1, Chang'e Ding2, Mengjie Tuo3
1Department of Gastroenterology, Jingmen Traditional Chinese Medicine Hospital, Jingmen 448000, China.
Background:
N6-methyladenosine (m6A) modification controls various processes during tumorigenesis. Although METTL3 functions as a pro-tumorigenic driver in esophageal squamous cell carcinoma (ESCC), its mechanisms are largely unknown.
Methods:
mRNA expression was detected by quantitative PCR, and protein expression was assessed by immunoblotting. Cell motility, invasiveness, and apoptosis were analyzed by wound-healing assay, transwell assay and flow cytometry, respectively. Cell ferroptosis was assessed by detecting the contents of ROS, MDA and Fe2+. The METTL3/PBX3 and PBX3/CA9 relationships were validated by luciferase, MeRIP or ChIP assay. The effect of METTL3 on tumor growth was tested by xenograft studies.
Results:
METTL3 was enhanced in ESCC tumors and cells, and its deficiency suppressed ESCC cell migration and invasion and promoted cell apoptosis and ferroptosis. Additionally, METTL3 deficiency caused growth inhibition of ESCC xenografts in vivo. METTL3 enhanced m6A modification of PBX3 mRNA. PBX3 was identified as a mediator of METTL3 function in modulating ESCC cell phenotypes. PBX3 promoted CA9 transcription, and METTL3 positively regulated CA9 through PBX3. PBX3 deficiency impeded ESCC cell migration and invasion and enhanced cell apoptosis and ferroptosis by downregulating CA9.
Conclusion:
Our study elucidates a novel mechanism, the METTL3/PBX3/CA9 cascade, underlying the oncogenic activity of METTL3 in ESCC. The novel cascade may represent the potential target for ESCC therapy in the future.
Related Concept Videos
Abnormal Proliferation
Mitogens and the Cell Cycle
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...

