IER3 Promotes Malignant Progression of Colorectal Cancer Through the NF-κB Pathway

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Colorectal cancer (CRC) is a major cause of cancer mortality globally.
• Metastasis and an immunosuppressive tumor immune microenvironment (TIME) are key challenges in CRC treatment.
• The role of the stress-responsive gene IER3 in CRC pathogenesis and immune modulation is not well understood.

Purpose of the Study:

• To investigate the functional role of IER3 in colorectal cancer progression.
• To explore IER3's impact on the tumor immune microenvironment.
• To identify IER3 as a potential therapeutic target and biomarker in CRC.

Main Methods:

• Integrated single-cell RNA sequencing (scRNA-seq) of clinical CRC samples.
• In vitro and in vivo functional studies to assess IER3's effects on CRC cells.
• Analysis of the TNF-α/NF-κB signaling pathway and immune cell interactions.

Main Results:

• A distinct IER3-expressing malignant subpopulation in CRC is associated with aggressive disease and poor prognosis.
• IER3 promotes CRC proliferation, invasion, and metastasis by activating the TNF-α/NF-κB pathway.
• IER3+ malignant cells induce an immunosuppressive TIME via altered immune cell infiltration and the FN1-CD44 axis.
• High IER3 expression correlates with reduced response to immune checkpoint blockade (ICB) and specific drug sensitivities.

Conclusions:

• IER3 is a critical mediator of both CRC progression and immune escape.
• IER3 represents a promising therapeutic target for colorectal cancer.
• IER3 expression levels may serve as a biomarker for predicting treatment response and guiding personalized therapy.