# NCKAP1 Inhibits the Progression of Renal Carcinoma via Modulating Immune Responses and the PI3K/AKT/mTOR Signaling Pathway

**Authors:** Xin Zhang, Jianqing Ye, Lixiang Sun, Wanli Xu, Xiaomeng He, Juan Bao, Jin Wang

PMC · DOI: 10.3390/ijms26062813 · International Journal of Molecular Sciences · 2025-03-20

## TL;DR

NCKAP1 helps stop kidney cancer by boosting immune responses and controlling a key signaling pathway.

## Contribution

This study reveals NCKAP1's role in renal cancer progression through immune modulation and the PI3K/AKT/mTOR pathway.

## Key findings

- Low NCKAP1 levels in renal cancer patients correlate with poor prognosis.
- NCKAP1 expression is linked to immune cell infiltration in kidney tumors.
- NCKAP1 suppresses cancer growth via the PI3K/AKT/mTOR pathway.

## Abstract

Nck-associated protein 1 (NCKAP1) is critical for cytoskeletal functions and various cellular activities, and deregulation of NCKAP1 in many cancers significantly influences the outcomes of malignant diseases. However, the functions of NCKAP1 in the progression of renal cancer are yet unknown. To investigate the specific roles of NCKAP1 in the immune regulation and tumor progression of renal cancer, the expression of NCKAP1 and genetic variations were analyzed across cancer types at different pathological stages via UALCAN and cBioPortal. Immune cell infiltration in renal cancer was also assessed by ssGSEA and single-cell gene expression data from the GEO. RNA sequencing of NCKAP1-overexpressing 769P cells further examined the impact of NCKAP1 on kidney cancer. Our pancancer analyses revealed a complex NCKAP1 expression profile across various cancer types, with reduced levels in renal cancer patients linked to patient prognosis. CIBERSORT and single-cell RNA sequencing revealed the expression patterns of NCKAP1 in different cell lineages in renal cancer and a significant correlation between NCKAP1 and immune cell infiltration in the kidney tumor microenvironment. We further verified that NCKAP1 suppressed cancer cell growth and affected tumor development in renal cancer via the PI3K/AKT/mTOR signaling pathway. Our results indicate that NCKAP1 is a potential predictive marker and treatment target for renal cancer.

## Linked entities

- **Genes:** NCKAP1 (NCK associated protein 1) [NCBI Gene 10787]
- **Diseases:** renal cancer (MONDO:0005206), kidney cancer (MONDO:0002367)

## Full-text entities

- **Genes:** MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, NCKAP1 (NCK associated protein 1) [NCBI Gene 10787] {aka HEM2, NAP1, NAP125, p125Nap1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}
- **Diseases:** cancer (MESH:D009369), kidney cancer (MESH:D007680), Renal Carcinoma (MESH:D002292)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** 769P — Homo sapiens (Human), Renal cell carcinoma, Cancer cell line (CVCL_1050)

## Full text

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## Figures

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## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC11942877/full.md

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Source: https://tomesphere.com/paper/PMC11942877