XTP8 Promotes Ovarian Cancer Progression by Activating AKT/AMPK/mTOR Pathway to Regulate EMT

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• Ovarian cancer (OC) is a leading cause of cancer death in women, characterized by high recurrence and metastasis rates.
• Hepatitis B virus X Ag-Transactivated Protein 8 (XTP8), a DEP domain-containing protein, is implicated in cancer cell growth and movement, but its role in OC is unknown.

Purpose of the Study:

• To investigate the role and mechanism of XTP8 in ovarian cancer progression.
• To identify downstream targets of XTP8 and elucidate its signaling pathways in OC.

Main Methods:

• Quantitative analysis of XTP8 expression in OC tissues.
• In vitro experiments involving XTP8 silencing and overexpression in OC cell lines.
• Western blotting to assess protein phosphorylation levels (AKT, AMPK, mTOR).
• Transcriptome sequencing to identify XTP8 downstream targets.

Main Results:

• XTP8 expression is elevated in ovarian cancer.
• XTP8 silencing inhibited proliferation and induced apoptosis, while overexpression had opposite effects.
• XTP8 promoted OC cell invasion and migration by inducing epithelial-mesenchymal transition (EMT).
• XTP8 modulated the AKT/AMPK/mTOR pathway, with Caldesmon (CALD1) identified as a downstream target.
• XTP8 and CALD1 collaboratively activate the AKT/AMPK/mTOR pathway, driving EMT and OC progression.

Conclusions:

• XTP8 acts as an oncogene in ovarian cancer by promoting EMT via the AKT/AMPK/mTOR pathway.
• The XTP8-CALD1 axis is crucial for ovarian cancer progression.
• Inhibiting the XTP8-CALD1 signaling axis presents a potential therapeutic target for ovarian cancer treatment.