ArticleJournal of experimental & clinical cancer research : CR2022
PCSK9 promotes the progression and metastasis of colon cancer cells through regulation of EMT and PI3K/AKT signaling in tumor cells and phenotypic polarization of macrophages.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers.
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Who cites it
177 citing papers in PubMed, 240 citations in OpenAlex.
- Whole-Genome Resequencing Reveals the Genetic Diversity and Adaptive Evolution ofEcology and evolution · 2026Article
- Role of PCSK9 in hallmarks of cancer: From mechanisms to interventions (Review).Oncology letters · 2026Review
- Lactylation Modification and Esophageal Cancer: Research Progress From Hypoxia-Induced Metabolic Reprogramming to Immune Escape.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Tumor-derived PCSK9-enriched exosomes reprogram adipocytes to drive metabolic dysregulation and immune evasion in triple-negative breast cancer.Cell death & disease · 2026Article
- Clinical implications of lactylation modification in digestive system tumors (Review).Oncology letters · 2026Review
- Aucubin inhibits epithelial-mesenchymal transition and angiogenesis in colorectal cancer via the HDAC6/PI3K/Akt signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- PCSK9 rs562556 variant and survival in BRCA1 mutation carriers and mutation-negative familial breast cancer.NPJ breast cancer · 2026Article
- Revisiting the Lipid-Cancer Axis: PCSK9, ANGPTL3, and CETP as Emerging Biomarkers and Therapeutic Targets in Oncology.Biomolecules · 2026Review
- CircLRIG1 inhibits the malignant phenotypes of colorectal cancer cells by inactivating the NF-κB signaling through interaction with FUS.Discover oncology · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Integrated single-cell and bulk transcriptomic analyses unveil a necroptosis-related prognostic model and its association with tumor microenvironment remodeling in gastric cancer.Discover oncology · 2026Article
- Lactylation in Colorectal Cancer: Regulatory Networks, Functional Mechanisms, and Clinical Translational Potential.International journal of molecular sciences · 2026Review
- Targeting USP14 enhances immunotherapy response by reprogramming tumor-associated macrophages in colon cancer.iScience · 2026Article
- Lipid metabolism as a central driver of immune remodeling and therapeutic vulnerability in metastatic colorectal cancer.Lipids in health and disease · 2026Review
- Lactate metabolism-driven lactylation: paradoxical modulation of intestinal inflammation and malignancy.Journal of translational medicine · 2026Review
- Neurochondrin drives colorectal cancer progression by modulating the PODXL-Ezrin axis and mitochondrial function.Cell death & disease · 2026Article
117 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is the ninth member of the proprotein convertase family that regulates lipoprotein homeostasis and altered PCSK9 expression was reportedly associated with tumor development and progression. This study assessed PCSK9 expression and functions in human colon cancer and then explored the underlying molecular events.
methodsColon cancer tissues were utilized for analysis of PCSK9 expression for association with clinicopathological factors from patients by immunohistochemistry assay. Manipulation of PCSK9 expression was assessed in vitro and in vivo for colon cancer cell proliferation, migration, and invasion using cell viability CCK-8, Transwell tumor cell migration and invasion, and wound-healing assays. Next, proteomic analysis, Western blot, qRT-PCR and Flow cytometry were conducted to assess downstream targets and tumor cell-derived PCSK9 action on macrophage polarization.
resultsPCSK9 expression was upregulated in colon cancer tissues versus the normal tissues, and associated with advanced tumor pathological grade. Knockdown of PCSK9 expression reduced colon cancer cell proliferation, migration, and invasion and suppressed tumor metastasis in vivo. PCSK9 directly or indirectly upregulated Snail 1 and in turn to downregulate E-cadherin expression, but upregulate N-cadherin and MMP9 levels and thereafter, to induce colon cancer cell epithelial-mesenchymal transition (EMT) process and activated PI3K/AKT signaling. However, PCSK9 overexpression showed the inverse effects on colon cancer cells. Knockdown of PCSK9 expression inhibited M2 macrophage polarization, but also promoted M1 macrophage polarization by reduction of lactate, protein lactylation and macrophage migration inhibitory factor (MIF) levels.
conclusionPCSK9 played an important role in the progression and metastasis of colon cancer by regulation of tumor cell EMT and PI3K/AKT signaling and in the phenotypic polarization of macrophages by mediating MIF and lactate levels. Targeting PCSK9 expression or activity could be used to effectively control colon cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.