Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.
Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.
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作者：
乳腺癌中的癌症干细胞（CSCs）已经被鉴定了近二十年。许多杰出的发现已经确立了CSCs在乳腺癌进展、转移和对治疗的抵抗中的重要功能。干细胞性是干细胞的特征性特征，其诱导和维持是由几条重要的信号通路决定的。靶向这些途径不可避免地具有挑战性，因为它们也与正常干细胞密切相关。在这里，我们将总结有关乳腺癌干细胞的文献，包括主要的信号通路，肿瘤微环境（TME）内的细胞相互作用和潜在的治疗意义。乳腺癌干细胞（BCSC）是乳腺癌中的一小部分细胞，具有自我更新、分化和重现肿瘤异质性的能力。临床上，BCSC与癌症进展、转移、复发和耐药性相关。BCSC的致瘤作用已经被广泛综述，但不会成为当前综述的主要焦点。在这里，我们的目标是强调关键的内在信号通路如何调节BCSC的命运，包括Wnt，Notch，Hedgehog和NF-κB信号通路，以及不同的细胞群如何与TME内的BCSC发生串扰，包括脂肪细胞，内皮细胞，成纤维细胞和免疫细胞。基于BCSCs的分子和细胞活性，我们还将总结BCSCs的靶向策略和相关的临床试验。这篇综述将强调乳腺癌中BCSC的发育受到BCSC内源性信号传导和TME中外部因素的影响，这为如何建立针对BCSC的乳腺癌治疗的综合治疗策略提供了见解。
Cancer stem cells (CSCs) in breast cancer have been identified for almost two decades. Many outstanding discoveries have established the important functions of CSCs in breast cancer progression, metastasis, and resistance to therapy. As the defining feature of CSCs, stemness is induced and maintained by several important signaling pathways. Targeting these pathways is inevitably challenging because they are also critically involved in normal stem cells. Here, we will summarize the literature on breast cancer stem cells, including major signaling pathways, cellular interactions within the tumor microenvironment (TME), and potential therapeutic implications. Breast cancer stem cells (BCSCs) constitute a small population of cells within breast cancer and are characterized by their ability to self-renew, differentiate, and recapitulate the heterogeneity of the tumor. Clinically, BCSCs have been correlated with cancer progression, metastasis, relapse, and drug resistance. The tumorigenic roles of BCSCs have been extensively reviewed and will not be the major focus of the current review. Here, we aim to highlight how the crucial intrinsic signaling pathways regulate the fate of BCSCs, including the Wnt, Notch, Hedgehog, and NF-κB signaling pathways, as well as how different cell populations crosstalk with BCSCs within the TME, including adipocytes, endothelial cells, fibroblasts, and immune cells. Based on the molecular and cellular activities of BCSCs, we will also summarize the targeting strategies for BCSCs and related clinical trials. This review will highlight that BCSC development in breast cancer is impacted by both BCSC endogenous signaling and external factors in the TME, which provides an insight into how to establish a comprehensively therapeutic strategy to target BCSCs for breast cancer treatments.
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DOI：
10.1126/science.aac9935
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Casey SC;Tong L;Li Y;Do R;Walz S;Fitzgerald KN;Gouw AM;Baylot V;Gütgemann I;Eilers M;Felsher DW
通讯作者：
Felsher DW
CCR7和Notch1轴之间的相互作用促进了MMTV-PYMT乳腺癌细胞中的干性。
影响因子：
37.3
作者：
Boyle ST;Gieniec KA;Gregor CE;Faulkner JW;McColl SR;Kochetkova M
通讯作者：
Kochetkova M
影响因子：
32.4
作者：
Agudo J;Park ES;Rose SA;Alibo E;Sweeney R;Dhainaut M;Kobayashi KS;Sachidanandam R;Baccarini A;Merad M;Brown BD
通讯作者：
Brown BD
影响因子：
21.3
作者：
Celià-Terrassa T;Liu DD;Choudhury A;Hang X;Wei Y;Zamalloa J;Alfaro-Aco R;Chakrabarti R;Jiang YZ;Koh BI;Smith HA;DeCoste C;Li JJ;Shao ZM;Kang Y
通讯作者：
Kang Y
DOI：
10.1158/1078-0432.ccr-16-1678
发表时间：
2017-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cecil DL;Slota M;O'Meara MM;Curtis BC;Gad E;Dang Y;Herendeen D;Rastetter L;Disis ML
通讯作者：
Disis ML