CCL20 triggered by chemotherapy hinders the therapeutic efficacy of breast cancer

被引：98

作者：

Chen, Weilong ^{[1
]}

Qin, Yuanyuan ^{[1
]}

Wang, Dong ^{[1
,2
,3
]}

Zhou, Lei ^{[1
,2
,3
]}

Liu, Yin ^{[4
]}

Chen, Sheng ^{[4
]}

Yin, Liang ^{[5
]}

Xiao, Yaoxing ^{[6
]}

Yao, Xiao-Hong ^{[7
,8
,9
]}

Yang, Xiaoli ^{[2
,3
]}

Ma, Wei ^{[2
,3
]}

Chen, Weifeng ^{[10
]}

He, Xueyan ^{[2
,3
]}

Zhang, Lixing ^{[2
,3
]}

Yang, Qifeng ^{[11
]}

Bian, Xiuwu ^{[7
,8
,9
]}

Shao, Zhi-ming ^{[2
,3
]}

Liu, Suling ^{[2
,3
]}

机构：

[1] Univ Sci & Technol China, CAS Key Lab Innate Immun & Chron Dis, Sch Life Sci, Hefei, Anhui, Peoples R China

[2] Fudan Univ, Shanghai Canc Ctr, Shanghai, Peoples R China

[3] Fudan Univ, Inst Biomed Sci, Innovat Ctr Cell Signaling Network,Canc Inst, Shanghai Med Coll,Key Lab Breast Canc Shanghai, Shanghai, Peoples R China

[4] Fudan Univ, Shanghai Med Coll, Dept Oncol, Dept Breast Surg, Shanghai, Peoples R China

[5] First Peoples Hosp Zhenjiang City, Dept Breast Surg, Zhenjiang, Peoples R China

[6] Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai, Peoples R China

[7] Third Mil Med Univ, Southwest Hosp, Inst Pathol, Chongqing, Peoples R China

[8] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing, Peoples R China

[9] Minist Educ China, Key Lab Tumor Immunopathol, Chongqing, Peoples R China

[10] Jiangnan Univ, Sch Food Sci & Technol, Natl Engn Res Ctr Funct Food, Wuxi, Peoples R China

[11] Shandong Univ, Qilu Hosp, Dept Breast Surg, Jinan, Shandong, Peoples R China

来源：

PLOS BIOLOGY | 2018年 / 16卷 / 07期

关键词：

MESENCHYMAL TRANSITION; CHEMOKINE CCL20; P-GLYCOPROTEIN; STEM-CELLS; KAPPA; PHARMACOKINETICS; CHEMORESISTANCE; ACTIVATION; RESISTANCE; MIGRATION;

D O I：

10.1371/journal.pbio.2005869

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 C zeta (PKC zeta) or p38 mitogen-activated protein kinase (MAPK)-mediated activation of p65 nuclear factor kappa B (NF-kappa B) pathway, significantly increasing the frequency and taxane resistance of BCSCs. Moreover, CCL20-promoted NF-kappa B 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-kappa B activation increased CCL20 expression, forming a positive feedback loop between NF-kappa B 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.

引用

页数：27

共 36 条

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