ArticleCancer science2022
TIMP1 promotes cell proliferation and invasion capability of right-sided colon cancers via the FAK/Akt signaling pathway.
Article in Cancer science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 46 citations in OpenAlex.
- Platelet-Related Signature in Colorectal Cancer: Prognosis and Therapy Guidance.International journal of molecular sciences · 2026Article
- Study on the expression, prognostic value, and molecular mechanisms of TIMP1 in glioma.Cancer gene therapy · 2026Article
- Nobiletin in the modified Yiqi Jianpi Decoction enhances the antitumor activity of CD8The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Identification of colorectal cancer molecular subtypes and prognostic features based on basement membrane-related genes.Journal of applied genetics · 2026Article
- A multi-omics prognostic model integrating disulfidptosis-related molecular features in colorectal cancer.Cancer cell international · 2026Article
- The Size of Glioblastoma Spheroids Influences Patterns of Invasion and Temozolomide Efficacy.Tissue engineering. Part C, Methods · 2026Article
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- TIMP1 expression in colorectal cancer: Linking prognosis, tumor immunity and molecular pathways.Oncology letters · 2026Article
- Necroptotic signaling orchestrates glioblastoma malignancy and potentiates temozolomide response.Cell death & disease · 2025Article
- Race-based differences in serum biomarkers for cancer-associated cachexia in a diverse cohort of patients with pancreatic ductal adenocarcinoma.Communications medicine · 2025Article
- Single-Cell and Bulk RNA Sequencing Reveal SPINK1 and TIMP1 as Epithelial Cell Marker Genes Linked to Colorectal Cancer Survival and Tumor Immune Microenvironment Profiles.International journal of molecular sciences · 2025Article
- Machine learning identifies inflammation-related diagnostic biomarkers for primary myelofibrosis with clinical validation.Scientific reports · 2025Article
- Integrative single-cell and bulk transcriptomes analyses reveal T cell-related prognostic risk model and tumor immune microenvironment modulation in colorectal cancer.Translational cancer research · 2025Article
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- Size-dependent invasion and therapeutic phenotype of 42MGBA glioblastoma spheroids.bioRxiv : the preprint server for biology · 2025Article
- Proteomics-based prognostic signature in colon adenocarcinoma patients with familial adenomatous polyposis.Translational cancer research · 2025Article
- Identifying Molecular Modulators of the Vascular Invasion in Rectal Carcinoma: Role ofInternational journal of molecular sciences · 2025Article
- Spatial transcriptomics of progression gene signature and tumor microenvironment leading to progression in mycosis fungoides.Blood advances · 2025Article
- Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer.Scientific reports · 2025Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although right-sided colorectal cancer (CRC) shows a worse prognosis than left-sided CRC, the underlying mechanism remains unclear. We established patient-derived organoids (PDOs) from left- and right-sided CRCs and directly compared cell proliferation and invasion capability between them. We then analyzed the expression of numerous genes in signal transduction pathways to clarify the mechanism of the differential prognosis. Cell proliferation activity and invasion capability in right-sided cancer PDOs were significantly higher than in left-sided cancer PDOs and normal PDOs, as revealed by Cell Titer Glo and transwell assays, respectively. We then used quantitative RT-PCR to compare 184 genes in 30 pathways among right-sided and left-sided cancer and normal PDOs and found that the TIMP1 mRNA level was highest in right-sided PDOs. TIMP1 protein levels were upregulated in right-sided PDOs compared with normal PDOs but was downregulated in left-sided PDOs. TIMP1 knockdown with shRNA significantly decreased cell proliferation activity and invasion capability in right-sided PDOs but not in left-sided PDOs. Moreover, TIMP1 knockdown significantly decreased pFAK and pAkt expression levels in right-sided PDOs but not in left-sided PDOs. A database analysis of The Cancer Genome Atlas revealed that TIMP1 expression in right-sided CRCs was significantly higher than in left-sided CRCs. Kaplan-Meier survival analysis showed significantly shorter overall survival in high-TIMP1 patients versus low-TIMP1 patients with right-sided CRCs but not left-sided CRCs. Our data suggest that TIMP1 is overexpressed in right-sided CRCs and promotes cell proliferation and invasion capability through the TIMP1/FAK/Akt pathway, leading to a poor prognosis. The TIMP1/FAK/Akt pathway can be a target for therapeutic agents in right-sided CRCs.
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