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T-cadherin and its impact on human diseases (Review)
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DOI：10.3892/mmr.2026.13820.png)
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Abstract
En 中文
Truncated-cadherin (T-cadherin) is a distinct glycosylphosphatidylinositol-anchored atypical cadherin that differs from classical cadherins since it does not have transmembrane and intracellular domains. It primarily functions as a dual receptor, serving as a physiological receptor for low-density lipoprotein (LDL) and a specific receptor for high-molecular-weight (HMW) adiponectin. Upon binding to LDL, T-cadherin activates calcium signaling, thereby promoting cell proliferation and migration and contributing to the development of atherosclerotic plaques. Conversely, its interaction with HMW adiponectin mediates cardiovascular protective effects through various mechanisms, such as increased exosome secretion, reduced intracellular ceramide accumulation, improved insulin sensitivity and anti-inflammatory actions. T-cadherin is predominantly expressed in cardiovascular tissues, such as endothelial cells, smooth muscle cells, pericytes and cardiomyocytes. Genetic polymorphisms in cadherin-13, the gene encoding T-cadherin, are notably associated with the risk of hypertension, type 2 diabetes and end-stage renal disease. In cancer, T-cadherin generally has tumor-suppressive effects, particularly in gastric, ovarian and breast cancers. This function is often compromised by promoter region hypermethylation, which leads to gene silencing and subsequently inhibits key signaling pathways, such as the PI3K/Akt, Wnt/beta-catenin and epithelial-mesenchymal transition pathways. The present review provided a comprehensive overview of the molecular mechanisms, regulation of expression and potential clinical importance of T-cadherin as a diagnostic biomarker and therapeutic target for cardiovascular diseases, including atherosclerosis, hypertension and heart failure, metabolic disorders, such as diabetes, and various cancers. Further research is required to fully elucidate the signal transduction pathways and competitive dynamics of T-cadherin ligand binding.
Keywords:
truncated-cadherin
adiponectin
low-density lipoprotein
cardiovascular disease
diabetes
cancer
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