ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Targeting SLITRK4 Restrains Proliferation and Liver Metastasis in Colorectal Cancer via Regulating PI3K/AKT/NFκB Pathway and Tumor-Associated Macrophage.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- SOX30 Facilitates Triple-Negative Breast Cancer Metastasis via TNFR2-NF-κB Signaling and Tumor Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- [High expression of CFL1 and phospho-CFL1 predicts poor prognosis and promotes migration of colon cancer cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- The genetic association of miR-34a-5p rs72631823 with the susceptibility to obstetric antiphospholipid syndrome.BMC women's health · 2026Article
- SPINK4 affected M2 macrophage polarization to promote colorectal cancer malignant phenotype by PI3K/AKT pathway.BMC cancer · 2026Article
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- A decade of progress in understanding LRRTM and Slitrk synaptic cell-adhesion molecules.Molecules and cells · 2026Review
- Lipid-Polymer Nanoparticles (LiPoNs) Mediated Codelivery of AntimiR-21 and Gadolinium Chelate in Triple Negative Breast Cancer Theranostics.Bioengineering (Basel, Switzerland) · 2026Article
- Network toxicology and Mendelian randomization reveal pathogenic factors of monoethyl phthalate-induced thyroid cancer.European thyroid journal · 2026Article
- NG25 Enhances Anti-Tumor Immunity inOncoTargets and therapy · 2026Article
- The hepatic macrophage: a key regulator of liver metastatic tumor microenvironment through cell crosstalk.Journal of translational medicine · 2025Review
- IL-1βJournal of neuroinflammation · 2025Article
- Liver metastasis of colorectal cancer: Mechanism and clinical therapy (Review).Oncology reports · 2025Review
- Review
- Multi-omics in colorectal cancer liver metastasis: applications and research advances.Cancer biology & medicine · 2025Review
- Targeting PTBP3-Mediated Alternative Splicing of COX11 Induces Cuproptosis for Inhibiting Gastric Cancer Peritoneal Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RAD23B Promotes Colorectal Cancer Metastasis via the Talin1/Integrin/PI3K/AKT/MMP9 Axis.Oncology research · 2025Article
- Immune microenvironment regulation and clinical immunotherapy strategies of metastatic liver cancer.Frontiers in immunology · 2025Review
- DDX49 as a novel prognostic biomarker regulates colorectal cancer cell proliferation through the TIMM44-PI3K-AKT pathway.Frontiers in oncology · 2025Article
- Targeting SLITRK4 Restrains Proliferation and Liver Metastasis in Colorectal Cancer via Regulating PI3K/AKT/NFκB Pathway and Tumor-Associated Macrophage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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17 authors.
Funding
Abstract
Liver metastasis is the major cause of death in colorectal cancer (CRC) due to the lack of effective treatment. To explore novel drivers of CRC liver metastasis, the transcriptomes of primary paracancerous, colorectal tumors and metastases from human patients are profiled. It is found that SLIT- and NTRK-like family member 4 (SLITRK4) is the top upregulated gene in liver metastases and is associated with worse overall survival of CRC patients. Multiple in vitro and in vivo models suggested SLITRK4 promoted CRC tumorigenesis, invasion, migration, and angiogenesis, and inhibition of it restrained CRC tumor growth and liver metastasis with a more profound effect on the tumor microenvironment (TME). Mechanistically, SLITRK4 overexpression significantly activated the PI3K/AKT/NFκB pathway, regulated extracellular matrix organization, and multiple cytokines expression. Furthermore, the results from coculture models and single-cell RNA sequencing analyses suggested SLITRK4 promoted tumor-associated macrophages (TAMs) infiltration and polarization. In addition, macrophage depletion significantly inhibited SLITRK4-induced liver metastasis in CRC. Finally, pharmacological inhibition of SLITRK4 by using lipid-polymer hybrid nanoparticles (NPs) for systemic siRNA delivery can effectively inhibit CRC liver metastasis. Taken together, these results pinpoint that SLITRK4 regulates CRC tumorigenesis and liver metastasis, and siRNA delivering NPs agents validate the therapeutic potential of targeting SLITRK4 in CRC.
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