IER3 Promotes Malignant Progression of Colorectal Cancer Through the NF‐κB Pathway
Zhigang Wei, Yinyi Luo, Yupeng Zhang, Qingxing Huang, Jianhang Shao, Yingying Zhang, Yuqi Zhang, Zhimin Wang, Chaojie Liang, Zhiyong Lai, Yongping Cui
TL;DR
This study shows that the IER3 gene promotes colorectal cancer growth and immune evasion through the NF-κB pathway, suggesting it could be a new treatment target.
Contribution
The study identifies IER3 as a novel driver of colorectal cancer progression and immune suppression via the NF-κB pathway.
Findings
IER3 expression is linked to aggressive colorectal cancer and poor prognosis.
IER3 activates the TNF-α/NF-κB pathway to enhance cancer proliferation and metastasis.
High IER3 levels correlate with reduced response to immune checkpoint blockade.
Abstract
Colorectal cancer (CRC) remains a leading cause of cancer‐related mortality worldwide, primarily due to metastatic progression and an immunosuppressive tumor immune microenvironment (TIME). The stress‐responsive gene IER3 is found to be dysregulated in multiple cancers. Currently, its functional role in CRC pathogenesis and immune modulation remains poorly understood. Here, using integrated single‐cell RNA sequencing (scRNA‐seq) of clinical samples, we identify a distinct IER3‐expressing malignant subpopulation associated with aggressive disease and poor prognosis. Functional studies demonstrate that IER3 drives CRC proliferation, invasion, and metastatic capacity both in vitro and in vivo. Mechanistically, IER3 activates the TNF‐α/NF‐κB signaling pathway, thereby enhancing the expression and phosphorylation of RELA/p65. Moreover, IER3+ malignant cells reshape the TIME into an…
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Taxonomy
TopicsCancer Immunotherapy and Biomarkers · Cancer-related molecular mechanisms research · Ferroptosis and cancer prognosis