ArticleCancer cell international2021
Cofilin-1, LIMK1 and SSH1 are differentially expressed in locally advanced colorectal cancer and according to consensus molecular subtypes.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 21 citations in OpenAlex.
- Exploring diarylheptanoid derivatives to target LIMK1 as potential agents against colorectal cancer.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Repurposing Cofilin-Targeting Compounds for Ischemic Stroke Through Cheminformatics and Network Pharmacology.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Cofilin(s) and Mitochondria: Function Beyond Actin Dynamics.International journal of molecular sciences · 2025Review
- Protective effect of compound K against podocyte injury in chronic kidney disease by maintaining mitochondrial homeostasis.Scientific reports · 2025Article
- Genes Co-Expressed withInternational journal of molecular sciences · 2024Article
- SSH3 promotes pancreatic cancer proliferation and migration by activating the notch signaling pathway.American journal of cancer research · 2024Article
- Prediction model for lymph node metastasis in superficial colorectal cancer: a better choice than computed tomography.Surgical endoscopy · 2023Article
- Loss of exosomal miR-200b-3p from hypoxia cancer-associated fibroblasts promotes tumorigenesis and reduces sensitivity to 5-Flourouracil in colorectal cancer via upregulation of ZEB1 and E2F3.Cancer gene therapy · 2023Article
- Novel Histopathological Biomarkers in Prostate Cancer: Implications and Perspectives.Biomedicines · 2023Review
- Paladin, overexpressed in colon cancer, is required for actin polymerisation and liver metastasis dissemination.Oncogenesis · 2022Article
- LIMK1: A promising prognostic and immune infiltration indicator in colorectal cancer.Oncology letters · 2022Article
- Multimetric feature selection for analyzing multicategory outcomes of colorectal cancer: random forest and multinomial logistic regression models.Laboratory investigation; a journal of technical methods and pathology · 2022Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundColorectal cancer (CRC) is among the deadliest cancers, wherein early dissemination of tumor cells, and consequently, metastasis formation, are the main causes of mortality and poor prognosis. Cofilin-1 (CFL-1) and its modulators, LIMK1/SSH1, play key roles in mediating the invasiveness by driving actin cytoskeleton reorganization in various cancer types. However, their clinical significance and prognostic value in CRC has not been fully explored. Here, we evaluated the clinical contribution of these actin regulators according to TNM and consensus molecular subtypes (CMSs) classification.
methodsCFL-1, LIMK1 and SSH1 mRNA/protein levels were assessed by real-time PCR and immunohistochemical analyses using normal adjacent and tumor tissues obtained from a clinical cohort of CRC patients. The expression levels of these proteins were associated with clinicopathological features by using the chi square test. In addition, using RNA-Seq data of CRC patients from The Cancer Genome Atlas (TCGA) database, we determine how these actin regulators are expressed and distributed according to TNM and CMSs classification. Based on gene expression profiling, Kaplan-Meier survival analysis was used to evaluated overall survival.
resultsBioinformatic analysis revealed that LIMK1 expression was upregulated in all tumor stages. Patients with high levels of LIMK1 demonstrated significantly lower overall survival rates and exhibited greater lymph node metastatic potential in a clinical cohort. In contrast, CFL-1 and SSH1 have expression downregulated in all tumor stages. However, immunohistochemical analyses showed that patients with high protein levels of CFL-1 and SSH1 exhibited greater lymph node metastatic potential and greater depth of local invasion. In addition, using the CMSs classification to evaluate different biological phenotypes of CRC, we observed that LIMK1 and SSH1 genes are upregulated in immune (CMS1) and mesenchymal (CMS4) subtypes. However, patients with high levels of LIMK1 also demonstrated significantly lower overall survival rates in canonical (CMS2), and metabolic (CMS3) subtypes.
conclusionsWe demonstrated that CFL-1 and its modulators, LIMK1/SSH1, are differentially expressed and associated with lymph node metastasis in CRC. Finally, this expression profile may be useful to predict patients with aggressive signatures, particularly, the immune and mesenchymal subtypes of CRC.
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