Study shows FAM111B overexpression enhances glioma malignancy via PI3K/AKT pathway, suggesting a novel treatment target

Gliomas are among the deadliest brain tumors, with limited treatment options and poor survival rates. Scientists from China identified FAM111B, a DNA-repair-associated protein, as a key driver of glioma progression. The study shows that FAM111B overexpression enhances tumor growth and aggressiveness by activating the PI3K/AKT pathway. This is the first research to link FAM111B to gliomas, offering a promising new biomarker and therapeutic target for this intractable disease.

Gliomas are the most prevalent and aggressive form of primary brain tumors in adults, with dismal survival rates despite surgery, radiation, and chemotherapy. Scientists continue to search for molecular drivers that could serve as new therapeutic targets. Now, researchers led by Dr. Quan Du from Zhejiang Chinese Medical University and Westlake University in China have identified a promising candidate: a protein known as FAM111B.

“Our findings revealed that FAM111B affected glioma malignancy by modulating the PI3K/AKT pathway,” highlights lead researcher Dr. Du. “This presents a new potential avenue for therapeutic intervention in the treatment of glioma.”

The study, published on May 19 2025, in the Chinese Neurosurgical Journal, is the first to examine the role of FAM111B in gliomas. Prior research had linked FAM111B to cell cycle regulation, DNA repair, and fibrosis-related diseases. However, its function in brain cancer was previously unknown.

Using genomic databases including The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), the research team found that FAM111B expression is significantly elevated in glioma tissues compared to healthy brain tissue. Moreover, higher expression levels correlated with older patient age, more advanced tumor grade, and poorer clinical outcomes—including reduced overall survival and disease-free survival. The authors confirmed these findings experimentally. Glioma cell lines and tumor samples showed significantly higher levels of FAM111B protein compared to normal tissues. When FAM111B was overexpressed in glioma cells, their proliferation, invasion, and migration dramatically increased. Conversely, knocking down FAM111B suppressed these malignant traits.

Further, in vivo experiments using mice confirmed FAM111B’s role in promoting tumor growth. Mice injected with glioma cells overexpressing FAM111B developed significantly larger and heavier tumors than controls.
To uncover the molecular mechanism behind these effects, the team conducted pathway enrichment analysis. Results pointed strongly to the PI3K/AKT signaling cascade—a pathway long associated with tumor growth and resistance to therapy. Further tests showed that FAM111B overexpression increased phosphorylation of PI3K and AKT, while silencing the protein had the opposite effect.

“FAM111B regulates glioma cell malignant features via the PI3K/AKT pathway,” the Dr. Du wrote. “These results support the hypothesis that FAM111B influences the malignant features of glioma cells primarily through the PI3K/AKT pathway.”Treatment with a PI3K inhibitor reversed the aggressive behavior caused by FAM111B overexpression, strongly suggesting a direct regulatory role. This not only strengthens the case for FAM111B as a key driver of glioma but also highlights it as a promising therapeutic target. The study's strength lies in its comprehensive approach, combining bioinformatics, cell culture, animal modeling, and molecular assays. However, the authors acknowledge the study’s limitations, particularly the small patient sample size and the need for broader validation across multiple research centers.
Nonetheless, the implications are significant. Identifying FAM111B as an independent prognostic marker and a key modulator of a known cancer pathway adds a valuable tool to the glioma research arsenal.

While therapies targeting the PI3K/AKT pathway already exist, this research may pave the way for more precise, FAM111B-guided interventions. “FAM111B has emerged not only as a critical biomarker for the development of glioma,” Dr Du concludes, “but also as a promising novel target for therapeutic intervention.”

As researchers work to solve the complex puzzle of brain cancer, FAM111B may soon take center stage.


***

Reference

Titles of original papers: The role of FAM111B in the malignant progression and molecular regulation of human glioma through the PI3K/Akt pathway

Journal: Chinese Neurosurgical Journal

DOI: 10.1186/s41016-025-00395-6