TFEB: a double-edged sword for tumor metastasis

Area of Science:

• Molecular Biology
• Cancer Research
• Cell Biology

Background:

• Transcription factor EB (TFEB) is a key regulator of cellular processes including autophagy and lysosome biogenesis.
• Tumor metastasis is a major challenge in cancer therapy, and the role of TFEB in this process is complex and debated.
• TFEB belongs to the microphthalmia-associated transcription factor (MiTF/TFE) family.

Purpose of the Study:

• To review and elucidate the multifaceted mechanisms by which TFEB regulates tumor metastasis.
• To discuss the contradictory roles of TFEB in promoting or inhibiting cancer cell metastasis.
• To explore the signaling pathways involved in TFEB activation and inactivation relevant to metastasis.

Main Methods:

• Literature review of studies investigating the role of TFEB in tumor metastasis.
• Analysis of TFEB's impact on autophagy, epithelial-mesenchymal transition (EMT), lysosomal biogenesis, lipid metabolism, and oncogenic signaling.
• Examination of TFEB regulation by pathways such as mTORC1, Rag GTPase, ERK2, and AKT.

Main Results:

• TFEB positively influences metastasis through autophagy, EMT, lysosomal biogenesis, lipid metabolism, and oncogenic signaling.
• Conversely, TFEB negatively impacts metastasis by affecting tumor-associated macrophages (TAMs) and EMT.
• Specific pathways regulating TFEB activation and inactivation (mTORC1, Rag GTPase, ERK2, AKT) are identified.

Conclusions:

• TFEB exhibits a dual role in tumor metastasis, with significant implications for therapeutic strategies.
• The precise mechanisms of TFEB-mediated metastasis regulation require further in-depth investigation.
• Understanding TFEB's complex functions is crucial for developing novel anti-metastasis treatments.