ArticleExperimental & molecular medicine2024
Cathepsin D promotes polarization of tumor-associated macrophages and metastasis through TGFBI-CCL20 signaling.
Article in Experimental & molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- PFAS is associated with perineural invasion in triple-negative breast cancer with a potential role for Cathepsin D dysregulation: a multi-omics and experimental study.Clinical and experimental medicine · 2026Article
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- Cutting to the core: Proteases in the tumor-bone interface and metastatic progression.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- A Degradomic Landscape of Proteolytic Remodeling in Melanoma Lung Metastasis.Journal of proteome research · 2026Article
- The contribution of phenolic endocrine-disrupting chemicals to breast cancer risk: A comprehensive bioinformatics analysis.Scientific reports · 2026Article
- DCC-2036 induces repolarization of TAMs to M1 type and enhances CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- TGFBI deficiency facilitates tumor associated macrophages M2 polarization and angiogenesis to promote pancreatic neuroendocrine neoplasms progression.Cancer cell international · 2026Article
- TGFBI in tumors and the tumor immune microenvironment: functional roles, mechanisms, and therapeutic targeting.Frontiers in immunology · 2026Review
- CCL20 mediates the effect of cathepsin S on hepatocellular carcinoma development insights from Mendelian randomization and bioinformatics analysis.Discover oncology · 2025Article
- CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Macrophages at the Crossroads of Chronic Stress and Cancer.International journal of molecular sciences · 2025Review
- Cathepsins: Emerging targets in the tumor ecosystem to overcome cancers.Seminars in cancer biology · 2025Review
- Protease regulation of tumor-immune cell symbiosis.Trends in cancer · 2025Review
- Article
- Defining gastric cancer ecology: the crucial roles of TREM2Communications biology · 2025Article
- Antibodies against the multifaceted cathepsin D protein open new avenues for TNBC immunotherapy.Journal for immunotherapy of cancer · 2025Article
- SHKBP1 is a target for sepsis: evidence from WGCNA and multiple machine learning algorithms.Frontiers in immunology · 2025Article
- Cleistanthin A derivative disrupts autophagy and suppresses head and neck squamous cell carcinoma progression via targeted vacuolar ATPase.Scientific reports · 2024Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
M2-like tumor-associated macrophages (TAMs) are risk factors for cancer progression and metastasis. However, the mechanisms underlying their polarization are still not fully understood. Although cathepsin D (Cat D) has been reported as a procarcinogenic factor, little is known about the functional role of Cat D in the tumor microenvironment (TME). This study aimed to explore the effect and molecular mechanisms of Cat D in the TME. Cat D knockout (KO) altered the cytokine secretion pattern and induced TAM reprogramming from the M2 to M1 subtype, thereby preventing epithelial-mesenchymal transition and tumor metastasis. Mechanistically, we identified transforming growth factor beta-induced protein (TGFBI) as a Cat D target protein that is specifically associated with TAM polarization. Elevated TGFBI expression in Cat D KO cancer cells resulted in a decline in M2-like TAM polarization. Our RNA-sequencing results indicated that the cancer cell-secreted chemokine CCL20 is a major secretory chemokine for Cat D-TGFBI-mediated TAM polarization. In contrast, Cat D overexpression accelerated TAM polarization into M2-like cells by suppressing TGFBI expression. In addition, the double Cat D and TGFBI KO rescued the inhibitory effects of Cat D KO on tumor metastasis by controlling TAM and T-cell activation. These findings indicated that Cat D contributes to cancer metastasis through TGFBI-mediated TAM reprogramming. Cat D deletion inhibits M2-like TAM polarization through TGFBI-mediated CCL20 expression, reprogramming the immunosuppressive TME. Our results open a potential new avenue for therapy focused on eliminating tumor metastasis.
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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 OpenQuestion graph.