Research suggests FKBP38’s role in suppressing tumor proliferation and metastasis via the mTOR pathway


A breakthrough study published on January 18, 2024, in the prestigious journal Archives of Biochemistry and Biophysics, DOI: 10.1016/, presents promising new findings that could change the course of endometrial cancer treatment. Researchers have identified the protein FK506-binding protein 38 (FKBP38) as a key suppressor of tumor growth and metastasis by interfering with the mammalian target of rapamycin (mTOR) signaling pathway.

Endometrial cancer (EC) stands as a common gynecological cancer with advanced-stage or recurrent cases often leading to high mortality rates due to the limitations of current treatment modalities. The groundbreaking investigation conducted by a dedicated team from the School of Biomedical and Pharmaceutical Sciences at Guangdong University of Technology revealed that FKBP38 might serve as a new target for therapeutic intervention in EC.

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The research team led by Prof. Xiaoli Wu and Dr. Fanghong Li performed a series of experiments to assess the function and mechanisms of FKBP38 in EC. The study comprised expression analyses, functional assays in cell cultures, and in vivo models to ascertain the role of FKBP38 in cancer metastasis and progression.

To begin with, the researchers observed FKBP38 expression levels in various EC cell lines including Ishikawa and AN3CA, with the former considered a low-grade and the latter a high-grade cell line. Remarkably, higher FKBP38 levels were detected in Ishikawa cells compared to AN3CA cells. This prompted further investigation into the potential of FKBP38 as a tumor suppressor.

Subsequent functional assays demonstrated that FKBP38 significantly hindered proliferation, migration, and invasion of EC cells. Interestingly, when FKBP38 was knocked down in Ishikawa cells, there was a substantial promotion of tumor growth in a subcutaneous xenograft model. Moreover, in a metastatic mouse model, lower FKBP38 expression resulted in an increased number of lung metastases originating from Hec-1-A cells, another EC cell line.

In an exploration of underlying mechanisms, the research demonstrated that FKBP38 suppressed several target proteins involved in the epithelial-to-mesenchymal transition (EMT) process, a key factor in cancer metastasis. Additionally, FKBP38 was found to reduce the phosphorylation of ribosomal S6 protein and eukaryotic initiation factor 4E-binding protein 1 (4EBP-1), both of which are important components of the mTOR pathway, suggesting a potent inhibition of this signaling route.

The inhibition of the mTOR pathway appeared to account for the observed reduction in EC cell proliferation, migration, and invasion post FKBP38 intervention. The researchers propose that FKBP38 exerts its tumor-suppressing role by directly modulating this critical signaling pathway, thus providing a potential focal point for new EC treatments.

The findings offer a new perspective on EC pathology and underscore the potential of FKBP38 as a prognostic biomarker and therapeutic target. Such revelations hold profound implications for improved patient outcomes in EC cases where resistance to traditional therapies poses a significant challenge.


The implications of this study extend into the clinical realm where FKBP38 could be leveraged for devising new treatment strategies tailored to counteract EC. The prospects of introducing FKBP38-targeted therapies hold much promise in the battle against gynecological malignancies. By adding another weapon in the oncologist’s arsenal, the hope is to transform the daunting prognosis associated with advanced-stage and recurrent EC into a more manageable and treatable condition.

Declaration of Interest
The authors declare no potential conflicts of interest regarding this study.


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1. Endometrial cancer treatment
2. FKBP38 and cancer
3. mTOR signaling pathway
4. Cancer cell metastasis
5. Targeted therapy for endometrial cancer