Calcium-Binding Protein S100P Promotes Tumor Progression but Enhances Chemosensitivity in Breast Cancer.
Calcium-Binding Protein S100P Promotes Tumor Progression but Enhances Chemosensitivity in Breast Cancer.
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DOI：
10.3389/fonc.2020.566302
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发表时间：
2020
影响因子：
4.7
通讯作者：
Qiao G
中科院分区：
文献类型：
--
作者：
Cong Y;Cui Y;Wang S;Jiang L;Cao J;Zhu S;Birkin E;Lane J;Ruge F;Jiang WG;Qiao G
化疗耐药仍然是乳腺癌治疗中需要克服的障碍之一。S100钙结合蛋白P （S100P）在多种癌症中被观察到过表达，并与耐药、转移和预后相关。然而，S100P在乳腺癌化疗耐药中的作用尚未完全确定。采用免疫组织化学方法对22对接受新辅助化疗的乳腺癌组织（化疗前和化疗后）进行S100P蛋白表达水平的评价。研究S100P对乳腺癌细胞生物学行为和化疗敏感性的影响。乳腺癌组织中S100P蛋白水平明显高于良性纤维腺瘤组织（p < 0.001）。新辅助化疗后S100P表达水平下降46.55% （p = 0.015）。亚组分析显示，S100P降低（57.58%）主要见于HER2+肿瘤（p = 0.027）。我们的体外实验表明，S100P的下调抑制了T47D和SK-BR-3乳腺癌细胞的增殖、粘附、迁移和侵袭能力。我们进一步证明，这种敲除增加了SK-BR-3细胞对紫杉醇和顺铂的化疗耐药。我们发现S100P通过上调NF-κB、CCND1和Vimentin发挥作用，下调E-cadherin。S100P促进乳腺癌细胞的侵袭性，可能被认为是一个有希望的治疗靶点。此外，S100P可用于预测HER2+乳腺癌患者化疗的治疗效果。
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. 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. 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. 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.
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影响因子：
--
作者：
Hsu YL;Hung JY;Liang YY;Lin YS;Tsai MJ;Chou SH;Lu CY;Kuo PL
通讯作者：
Kuo PL
影响因子：
5.2
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Mueller-Tidow, Carsten