CCL20 triggered by chemotherapy hinders the therapeutic efficacy of breast cancer.
CCL20 triggered by chemotherapy hinders the therapeutic efficacy of breast cancer.
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化疗引发的CCL20阻碍乳腺癌的治疗效果
DOI：
10.1371/journal.pbio.2005869
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发表时间：
2018-07
期刊：
影响因子：
9.8
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Chen W;Qin Y;Wang D;Zhou L;Liu Y;Chen S;Yin L;Xiao Y;Yao XH;Yang X;Ma W;Chen W;He X;Zhang L;Yang Q;Bian X;Shao ZM;Liu S
三阴性乳腺癌（TNBC）的化疗耐药给患者生存率的提高带来了巨大的挑战。TNBC中紫杉烷化学耐药的机制尚未得到很好的研究。我们的研究结果表明，C-C基序趋化因子配体20 （CCL20）在含紫杉烷的乳腺癌非病理性完全缓解患者化疗期间显著升高。此外，CCL20通过蛋白激酶Cζ (PKCζ)或p38丝裂原活化蛋白激酶（MAPK）介导的p65核因子κB （NF-κB）通路激活，促进乳腺癌干细胞（BCSCs）或乳腺癌干细胞样细胞的自我更新和维持，显著增加BCSCs的频率和紫杉醇耐药。此外，ccl20促进的NF-κB活化增加了atp结合盒B亚家族成员1 (ABCB1)/多药耐药1 （MDR1）的表达，导致紫杉烷的细胞外外排。这些结果表明，化疗诱导的CCL20通过上调ABCB1介导化疗耐药。此外，NF-κB活化增加了CCL20的表达，在NF-κB和CCL20通路之间形成了正反馈回路，为乳腺癌细胞的化疗耐药提供了持续的动力。我们的研究结果表明，CCL20可能是一种新的紫杉烷反应预测标志物，阻断CCL20或其下游途径可能逆转乳腺癌患者紫杉烷耐药。
Chemotherapeutic resistance in triple-negative breast cancer (TNBC) has brought great challenges to the improvement of patient survival. The mechanisms of taxane chemoresistance in TNBC have not been well investigated. Our results illustrated C-C motif chemokine ligand 20 (CCL20) was significantly elevated during taxane-containing chemotherapy in breast cancer patients with nonpathologic complete response. Furthermore, CCL20 promoted the self-renewal and maintenance of breast cancer stem cells (BCSCs) or breast cancer stem-like cells through protein kinase Cζ (PKCζ) or p38 mitogen-activated protein kinase (MAPK)-mediated activation of p65 nuclear factor kappa B (NF-κB) pathway, significantly increasing the frequency and taxane resistance of BCSCs. Moreover, CCL20-promoted NF-κB activation increased ATP-binding cassette subfamily B member 1 (ABCB1)/multidrug resistance 1 (MDR1) expression, leading to the extracellular efflux of taxane. These results suggested that chemotherapy-induced CCL20 mediated chemoresistance via up-regulating ABCB1. In addition, NF-κB activation increased CCL20 expression, forming a positive feedback loop between NF-κB and CCL20 pathways, which provides sustained impetus for chemoresistance in breast cancer cells. Our results suggest that CCL20 can be a novel predictive marker for taxane response, and the blockade of CCL20 or its downstream pathway might reverse the taxane resistance in breast cancer patients.
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影响因子：
5.6
作者：
Marsigliante, Santo;Vetrugno, Carla;Muscella, Antonella
通讯作者：
Muscella, Antonella
DOI：
10.1001/jama.2011.593
发表时间：
2011-05-11
期刊：
JAMA
影响因子：
--
作者：
Hatzis C;Pusztai L;Valero V;Booser DJ;Esserman L;Lluch A;Vidaurre T;Holmes F;Souchon E;Wang H;Martin M;Cotrina J;Gomez H;Hubbard R;Chacón JI;Ferrer-Lozano J;Dyer R;Buxton M;Gong Y;Wu Y;Ibrahim N;Andreopoulou E;Ueno NT;Hunt K;Yang W;Nazario A;DeMichele A;O'Shaughnessy J;Hortobagyi GN;Symmans WF
通讯作者：
Symmans WF
影响因子：
3.8
作者：
Pusztai, L;Mendoza, TR;Hortobagyi, GN
通讯作者：
Hortobagyi, GN
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
254.7
作者：
DeSantis, Carol E.;Fedewa, Stacey A.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin