TFEB translocation

In this study, we loaded the anticancer drug doxorubicin (DOX) and an MRI contrast agent into silica nanoparticles, coating them with pH-responsive and tumor cell-targeting polymers...Additionally, we demonstrated that the nanocarrier inhibits autophagic flux in liver cancer cells by targeting the autophagy-lysosome pathway and regulating the nuclear translocation of TFEB, thereby promoting tumor cell death. This novel diagnostic-integrated nanocarrier is expected to be a promising tool for targeted liver cancer treatment.

Furthermore, repression of mTORC1 results in a basal-like breast cancer cell phenotype and disruption of ductal carcinoma in situ (DCIS)-like organization in a tumor xenograft model. Altogether, our data call for revaluation of mTOR inhibitors in breast cancer therapy.

JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; 22(6): 697-709.

These results identify sertraline and indatraline as immunostimulatory agents for cancer treatment. More generally, this research shed light on novel therapeutic avenues harnessing lysosomal cholesterol transport to regulate immunogenic cell death.

P2, N=15, Active, not recruiting, National Cancer Institute (NCI) | N=40 --> 15 | Trial completion date: Sep 2027 --> Nov 2025 | Trial primary completion date: Sep 2027 --> Sep 2024

Bortezomib effectively inhibits MM cell proliferation and induces autophagy, partly through TFEB-mediated mechanisms, with potential involvement of the MAPK pathway.

Overall, our study demonstrates the key role of circEGFR in autophagy, malignant progression, and metastasis of TNBC. These indicate circEGFR is a potential diagnosis biomarker and therapeutic target for TNBC.

Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury.

In a melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors with no recurrences observed in mice. Therefore, cholesterol reduction is a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2023 --> Sep 2027 | Trial primary completion date: Sep 2023 --> Sep 2027

Taken together, PTPRC knockdown-mediated TFEB phosphorylation and translocation dramatically promoted lysosome biogenesis, ferritinophagy, as well as the ferroptosis of OS cells via regulating FTH1/FTL signaling. Therefore, PTPRC/TFEB/FTH1 signaling may be a potential target for OS.

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2031 --> Sep 2023 | Trial primary completion date: Jun 2031 --> Sep 2023