Single-cell RNA sequencing identifies ZBP1-dependent mechanisms in OSCC progression.

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with a poor prognosis, significantly influenced by its complex tumor microenvironment.
• Cancer-associated fibroblasts (CAFs) are key players in OSCC progression, mediating tumor development through secreted signaling molecules.

Purpose of the Study:

• To elucidate the molecular mechanism by which Z-DNA-binding protein 1 (ZBP1) promotes OSCC development via CAF regulation.
• To investigate the role of the ZBP1-CCL7/CCR1 signaling axis in mediating communication between CAFs and OSCC cells.

Main Methods:

• Establishment of orthotopic MOC1 transplantation and 4NQO-induced OSCC models in Zbp1 knockout mice.
• Single-cell RNA sequencing (scRNA-seq) for cellular heterogeneity and signaling analysis.
• In vitro CAF induction and Transwell co-culture systems, followed by in vivo rescue and antagonist experiments.

Main Results:

• ZBP1 deficiency in mice led to reduced OSCC growth, proliferation, and downregulation of proliferation-related pathways.
• scRNA-seq revealed significant attenuation of the CCL7-CCR1 signaling axis between CAFs and tumor cells in Zbp1-deficient models.
• ZBP1 was found to regulate CCL7 expression in CAFs, impacting CAF-mediated promotion of tumor cell proliferation, migration, and invasion.

Conclusions:

• ZBP1 is crucial for OSCC progression, acting as a bridge for CAF-tumor cell communication through the CCL7-CCR1 axis.
• Targeting the ZBP1-CCL7/CCR1 signaling pathway presents a potential therapeutic strategy for OSCC.