Cluster of differentiation 147 mediates chemoresistance in breast cancer by affecting vacuolar H+-ATPase expression and activity

Abstract

Abstract. Vacuolar H + -ATPase (V-ATPase) serves a key role in adjusting and maintaining the intracellular pH, as well as in regulating the drug resistance of tumor cells. In recent years, the expression level of V-ATPase has been considered to be able to predict the sensitivity of breast cancer cells to chemotherapy drugs. Cluster of differentiation 147 (CD147) is known to serve a key role in the development and progression of breast cancer. The present study aimed to identify the role CD147 and V-ATPase in chemoresistance in breast cancer, and to characterize the regulation of CD147 on V-ATPase. Firstly, the expression levels of CD147 and V-ATPase were detected in chemotherapy-resistance breast cancer samples. It was demonstrated that V-ATPase was highly expressed in chemotherapy-resistance breast cancer samples, and that its expression was correlated with CD147 expression. Subsequently, MCF-7 and MDA-MB-231 cells were used to study the regulatory effect of CD147 on the expression and function of V-ATPase. Gene transfection or small interfering RNA transfection were used to control the expression of CD147 in the two cell lines. The results revealed that the overexpression of CD147 increased the expression of V-ATPase in MCF-7 cells, whereas CD147 knockdown decreased V-ATPase expression in MDA-MB-231 cells. It was also observed that CD147 affected the V-ATPase activity, regulating the transmembrane pH gradient of cancer cells. These results demonstrated that CD147 was associated with the sensitivity of chemotherapeutic drugs of epirubicin and docetaxel, while pantoprazole was able to partially reverse the CD147-mediated chemoresistance in breast cancer. Therefore, the current study provided a possible mechanism for further examination of drug resistance in breast cancer.

CD147: an integral and potential molecule to abrogate hallmarks of cancer

“…In that light, determining a molecule common across heterotypic cancer types, cancer characteristics, and neoplastic signal transductions would provide a viable hotspot with an explosive anti-cancer effect. Apart from being involved in cancer development, progression, metastasis, and recurrence, CD147 has also been associated with resistance to multiple anti-cancer therapies such as Temozolomide (89), Cisplatin (90), Oxaliplatin (91), Biguanides (Metformin) (92), Doxorubicin (93), Ara-C (Cytarabine) (80), Gemcitabine (86), Paclitaxel (94), Epirubicin (95), Docetaxel (96), Vemurafenib (97), and Radiotherapy (48); exhibited in gliomas, carcinomas of the Larynx, lung, breast, gastric, liver, pancreas, colon, bladder, prostate, ovary, and cervical; melanoma, and lymphomas (Figure 2). Nevertheless, inhibition of CD147 activities in these studies rendered the cancer cells sensitive to the treatments.…”

Investigating underlying human immunity genes, implicated diseases and their relationship to COVID-19

“…CD147 (CD147; ENSG00000172270) is a protein proven to be an important receptor on red blood cells and a key molecule involved in the interaction between hepatocellular carcinoma cells and hematopoietic stem cells. CD147 is involved in a variety of biological processes and diseases including breast cancer, thyroid carcinoma, ameloblastoma, ascending cholangitis, grade III astrocytoma, Newcastle disease, necrotizing ulcerative gingivitis, mucolipidosis-III alpha/beta, accommodative esotropia, tongue squamous cell carcinoma, tumor invasion, metastasis, angiogenesis, energy metabolism, multidrug resistance and COVID-19 [ 53 , 54 ].…”

CD83 Receptor Unveiled as a Therapeutic Target in Metastatic Breast Cancer through Single-Cell RNA-Seq

“…Cluster of Differentiation (CD) proteins emerge as key players influencing tumor development, metastasis, and therapeutic responses. CD proteins in breast cancer signify their multifaceted roles in diagnosis [2], prognosis [3], immune modulation [4], targeted therapy [5], metastasis [6], and treatment resistance [7]. Importantly, while some CD proteins may promote metastasis, others may act as tumor suppressors, inhibiting the spread of cancer cells.…”