COL10A1 overexpression potentially contributes to poor outcomes in breast cancer via autophagy and vasculogenic mimicry.

Background: Although the in-depth study of breast cancer pathogenesis has led to progress in therapies and improved outcomes in recent decades, new treatment methods are needed, especially for incurable metastatic breast cancer. Studies have proven that collagen X alpha 1 chain (COL10A1) expression is elevated in various malignant tumors, but COL10A1 has not been systematically analyzed in breast cancer. We investigated the effects of COL10A1 on breast cancer development and the mechanisms involved. Methods: We analyzed COL10A1 expression through the cancer database, and collected serum and tumour tissue specimens from patients with breast cancer to evaluate COL10A1's expression and correlation with clinicopathology. COL10A1 expression in breast cancer cell lines was assessed at the cellular level, and stable transient cell lines were constructed for autophagy examination in breast cancer cells using immunofluorescence and Western blotting. Tubulation assay and Western blotting were used to detect changes in vasculogenic mimicry (VM). Different experiments evaluated COL10A1's effects on breast cancer cell proliferation, migration, and invasiveness. A subcutaneous transplantation nude mouse tumor model was constructed, and changes in tumor volume and mass were recorded, while changes in the expression of vascular growth mimetic genes were examined using Western blotting. Results: Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases revealed COL10A1 upregulation in different breast cancer subtypes. Kaplan-Meier Plotter analysis showed that patients with elevated COL10A1 expression had poorer survival. Clinical tests found that COL10A1 expression in tumor specimens from patients with breast cancer was significantly higher than in controls and was closely associated with clinicopathology features, such as histological grading, tumor-node-metastasis (TNM) stage, and distant lymph node metastasis. Western blot analysis and other experiments revealed that low COL10A1 expression inhibited autophagy and VM in breast cancer cells, which inhibited breast cancer proliferation, apoptosis, migration, and invasion. High COL10A1 expression had opposite effects. Animal experiments showed that tumors from the high COL10A1 expression group were significantly larger than those from the control group. Conclusions: COL10A1 may be involved in breast cancer cell proliferation, apoptosis, invasion and migration, which are related to autophagy and VM, suggesting that COL10A1 may serve as a novel target for clinical breast cancer therapy.