Calcium-Binding Protein S100P Promotes Tumor Progression but Enhances Chemosensitivity in Breast Cancer

Abstract

Background: Chemoresistance remains one of the obstacles to overcome in the treatment of breast cancer. S100 calcium-binding protein P (S100P) has been observed to be overexpressed in several cancers and has been associated with drug resistance, metastasis, and prognosis. However, the role of S100P in chemoresistance in breast cancer has not been thoroughly determined. Methods: Immunohistochemistry was used to evaluate the expression level of S100P protein in 22 pairs (pre-chemo and post-chemo) of breast cancer tissue from patients who underwent neoadjuvant chemotherapy. The influence of S100P on the biological behavior and chemosensitivity of breast cancer cells was then investigated. Results: The protein level of S100P in breast cancer tissue was significantly higher than in benign fibroadenoma (p < 0.001). The S100P expression level was shown to be decreased by 46.55% after neoadjuvant chemotherapy (p = 0.015). Subgroup analysis revealed that S100P reduction (57.58%) was mainly observed in the HER2+ tumors (p = 0.027). Our in vitro experiments showed that the knockdown of S100P suppressed the proliferation, adhesion, migrative and invasive abilities of T47D and SK-BR-3 breast cancer cells. We further demonstrated that this knockdown increased the chemoresistance to paclitaxel and cisplatin in SK-BR-3 cells. We found S100P exerted its function by upregulating NF-κB, CCND1 and Vimentin, but downregulating E-cadherin. Conclusion: S100P promotes the aggressive properties of breast cancer cells and may be considered as a promising therapeutic target. Moreover, S100P can be used to predict the therapeutic effect of chemotherapy in HER2+ breast cancer patients.

S100A16 promotes acute kidney injury by activating HRD1-induced ubiquitination and degradation of GSK3β and CK1α

“…The C-terminal EF helix structure consists of a typical Ca 2+ -binding loop formed by 12 amino acids, while the N-terminal EF helix structure contains 14 S100 protein-specific amino acids [ 38 ]. The S100 protein is involved in a range of biological processes, and S100 protein is also associated with multiple diseases, such as inflammation, neurodegenerative diseases, depression, Down's syndrome, cystic fibrosis, and cancers [ 39 ]. Multiple members of the S100 family are markers of certain tumors, such as S100A7, S100A13, S100A14 [ 19 , 20 ].…”

S100A16 Promotes Acute Kidney Injury By Activating HRD1-Induced Ubiquitination And Degradation of GSK3β And CK1α

“…The C-terminal EF helix structure consists of a typical Ca 2+ -binding loop formed by 12 amino acids, while the N-terminal EF helix structure contains 14 S100 protein-speci c amino acids [35]. The S100 protein are involved in a range of biological processes, and S100 protein is also associated with multiple diseases, such as in ammation, neurodegenerative diseases, depression, Down's syndrome, cystic brosis, and cancers [36]. Multiple members of the S100 family are markers of certain tumors, such as S100A7, S100A13, S100A14 [19,20].…”

Aberrant calcium signalling downstream of mutations in TP53 and the PI3K/AKT pathway genes promotes disease progression and therapy resistance in triple negative breast cancer

“…Proteins such as S100P are also linked to TP53, where their expression was found to be altered in BC, enabling drug resistance [82] . Specifically, the expression of S100P is elevated in TNBC and linked to chemotherapy resistance and poor survival [83][84][85][86] .…”