CYP1B1 Augments the Mesenchymal, Claudin-Low, and Chemoresistant Phenotypes of Triple-Negative Breast Cancer Cells.
CYP1B1 Augments the Mesenchymal, Claudin-Low, and Chemoresistant Phenotypes of Triple-Negative Breast Cancer Cells.
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CYP1B1增强了三阴性乳腺癌细胞的间充质、低claudin和耐药表型。
DOI：
10.3390/ijms23179670
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发表时间：
2022-08-26
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞色素P4501 B1（CYP 1B 1）在乳腺癌中升高。研究表明CYP 1B 1与侵袭性癌症表型之间存在关系。在这里，我们报告在三阴性乳腺癌细胞系，其中敲低（KD）的CYP 1B 1的体外研究，以确定其表达对侵袭性细胞表型的影响。MDA-MB-231细胞中的CYP 1B 1 KD导致间充质形态的丧失、上皮-间充质基因的表达改变以及紧密连接蛋白（CLDN）RNA和蛋白质的增加。CYP 1B 1 KD细胞的细胞间接触和细胞旁屏障功能增加，细胞增殖速率降低，迁移和侵袭活性消失，球状体形成减少。对临床乳腺癌肿瘤样本的分析显示，肿瘤表现出较高的CYP 1B 1 RNA水平与总体和无病生存期减少之间存在相关性。CYP 1B 1的肿瘤表达与CLDN 7表达呈负相关，CYP 1B 1 HI/CLDN 7 LOW鉴定出中位生存期较低的患者。具有CYP 1B 1 KD的细胞对紫杉醇、5-氟尿嘧啶和顺铂的化疗敏感性增强。我们的发现，CYP 1B 1 KD可以增加化疗敏感性，这表明该酶的治疗靶向。CYP 1B 1抑制剂联合化疗药物可能为针对某些形式的高转移性乳腺癌的辅助或新辅助治疗提供一种新的靶向和有效的方法。
Cytochrome P4501B1 (CYP1B1) is elevated in breast cancer. Studies indicate a relationship between CYP1B1 and aggressive cancer phenotypes. Here, we report on in vitro studies in triple-negative breast cancer cell lines, where knockdown (KD) of CYP1B1 was used to determine the influence of its expression on invasive cell phenotypes. CYP1B1 KD in MDA-MB-231 cells resulted in the loss of mesenchymal morphology, altered expression of epithelial–mesenchymal genes, and increased claudin (CLDN) RNA and protein. CYP1B1 KD cells had increased cell-to-cell contact and paracellular barrier function, a reduced rate of cell proliferation, abrogation of migratory and invasive activity, and diminished spheroid formation. Analysis of clinical breast cancer tumor samples revealed an association between tumors exhibiting higher CYP1B1 RNA levels and diminished overall and disease-free survival. Tumor expression of CYP1B1 was inversely associated with CLDN7 expression, and CYP1B1HI/CLDN7LOW identified patients with lower median survival. Cells with CYP1B1 KD had an enhanced chemosensitivity to paclitaxel, 5-fluorouracil, and cisplatin. Our findings that CYP1B1 KD can increase chemosensitivity points to therapeutic targeting of this enzyme. CYP1B1 inhibitors in combination with chemotherapeutic drugs may provide a novel targeted and effective approach to adjuvant or neoadjuvant therapy against certain forms of highly metastatic breast cancer.
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影响因子：
3.7
作者：
Dias K;Dvorkin-Gheva A;Hallett RM;Wu Y;Hassell J;Pond GR;Levine M;Whelan T;Bane AL
通讯作者：
Bane AL
影响因子：
12.3
作者：
Herschkowitz JI;Simin K;Weigman VJ;Mikaelian I;Usary J;Hu Z;Rasmussen KE;Jones LP;Assefnia S;Chandrasekharan S;Backlund MG;Yin Y;Khramtsov AI;Bastein R;Quackenbush J;Glazer RI;Brown PH;Green JE;Kopelovich L;Furth PA;Palazzo JP;Olopade OI;Bernard PS;Churchill GA;Van Dyke T;Perou CM
通讯作者：
Perou CM
影响因子：
8
作者：
Bhat AA;Pope JL;Smith JJ;Ahmad R;Chen X;Washington MK;Beauchamp RD;Singh AB;Dhawan P
通讯作者：
Dhawan P
影响因子：
16.6
作者：
Fougner, Christian;Bergholtz, Helga;Sorlie, Therese
通讯作者：
Sorlie, Therese
影响因子：
10.7
作者：
Mohamed, Hossam T.;Gadalla, Ramy;Mohamed, Mona M.
通讯作者：
Mohamed, Mona M.