Collagen Type X Alpha 1 (COL10A1) Contributes to Cell Proliferation, Migration, and Invasion by Targeting Prolyl 4-Hydroxylase Beta Polypeptide (P4HB) in Breast Cancer

Abstract

Background Breast cancer, a common malignant tumor, has been considered as the leading cause of cancer-related death in women. Collagen type X alpha 1 (COL10A1) is overexpressed in breast cancer. The current study was designed to determine the functional involvement and regulatory mechanism of COL10A1 on the growth and metastasis of breast cancer. Material/Methods COL10A1 and Prolyl 4-hydroxylase beta polypeptide (P4HB) expressions in normal tissues and tumor tissues of breast cancer patients were obtained from the GEPIA dataset. COL10A1 and P4HB levels in breast cancer cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Furthermore, the interaction between COL10A1 and P4HB was confirmed by co-immunoprecipitation (Co-IP) assay. Cell Counting Kit-8 (CCK-8) and colony formation assay were applied to evaluate cell proliferation and clone-forming abilities of breast cancer cells. In addition, wound healing assay and transwell assay were performed to measure cell migration and invasion capabilities, respectively, in breast cancer. Results The GEPIA dataset presented overexpressed COL10A1 and P4HB in tumor tissues of breast cancer patients. COL10A1 and P4HB expression levels were greatly upregulated in breast cancer cell lines. In addition, COL10A1 could directly interact with P4HB. Functionally, overexpressed COL10A1 boosted the proliferation and metastasis of breast cancer cells and silenced COL10A1 impeded the progression of breast cancer. More importantly, knockdown of P4HB weakened the promoting effects of overexpressed COL10A1 on cell proliferation, migration, and invasion in breast cancer. Conclusions COL10A1 promotes the malignant progression of breast cancer by upregulating P4HB expression, indicating that COL10A1 functions as an oncogene in breast cancer.

Plasma Proteome Signature to Predict the Outcome of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

“…These findings indicate that P4HB may serve as a potential molecular marker for the diagnosis and treatment of cancer. We demonstrated that low serum P4HB level is significantly associated with better DFS and OS, which is consistent with the findings reported by Yang et al [ 105 ]. The study demonstrated that downregulation of P4HB represses the promoting effects of overexpressed COL10A1 on the proliferation, migration, and invasion of BC cells and, conversely, upregulation of P4HB promotes BC cell proliferation and clone-forming ability, as well as increasing BC cell migration and invasion [ 105 ].…”

The role of network‐forming collagens in cancer progression

“…COL4A2 knockdown can reduce triple‐negative breast cancer cells migration and proliferation, suggesting that COL4A2 may be a target for the treatment of triple‐negative breast cancer 65 . In addition, the interaction between COL10A1 and prolyl 4‐hydroxylase possibly regulates the proliferation, migration and invasion of breast cancer cells 66 …”

High expression of transmembrane P24 trafficking protein 9 predicts poor prognosis in breast carcinoma

“…On the other hand, PPIB, a peptidylpropyl isomerase, participated in colorectal cancer progression and chemoresistance [49]. Studies have also suggested that P4HB may extensively regulate tumor progression and prognosis of patients with cancer [50][51][52][53][54], including BRCA [55,56]. In BRCA, TMED9 may affect cancer progression and prognosis by interacting with these proteins.…”