Calcium-binding protein S100P promotes tumor progression

22 Background: Chemoresistance remains one of the obstacles to overcome in the treatment of 23 breast cancer. S100 calcium-binding protein P (S100P) has been observed to be overexpressed 24 in several cancers and has been associated with drug resistance, metastasis, and prognosis. 25 However, the role of S100P in chemoresistance in breast cancer has not been thoroughly 26 determined. Methods: Immunohistochemistry was used to evaluate the expression level of 27 S100P protein in 22 pairs (pre-chemo and post-chemo) of breast cancer tissue from patients 28 who underwent neoadjuvant chemotherapy. The influence of S100P on the biological behavior 29 and chemosensitivity of breast cancer cells was then investigated. Results: The protein level 30 of S100P in breast cancer tissue was significantly higher than in benign fibroadenoma 31 (p<0.001). The S100P expression level was shown to be decreased by 46.55% after 32 neoadjuvant chemotherapy (p=0.015). Subgroup analysis revealed that S100P reduction 33 (57.58%) was mainly observed in the HER2+ tumors (p=0.027). Our in-vitro experiments 34 showed that the knockdown of S100P suppressed the proliferation, adhesion, migrative and 35 invasive abilities of T47D and SK-BR-3 breast cancer cells. We further demonstrated that this 36 knockdown increased the chemoresistance to paclitaxel and cisplatin in SK-BR-3 cells. We 37 found S100P exerted its function by upregulating NF-κB, CCND1 and Vimentin, but 38 downregulating E-cadherin. Conclusions: S100P promotes the aggressive properties of breast 39 cancer cells and may be considered as a promising therapeutic target. Moreover, S100P can be 40 used to predict the therapeutic effect of chemotherapy in HER2+ breast cancer patients. 41