Upregulation of S100A10 in metastasized breast cancer stem cells.
Upregulation of S100A10 in metastasized breast cancer stem cells.
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DOI：
10.1111/cas.14659
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发表时间：
2020-12
期刊：
影响因子：
5.7
通讯作者：
Shimono Y
中科院分区：
文献类型：
--
作者：
Yanagi H;Watanabe T;Nishimura T;Hayashi T;Kono S;Tsuchida H;Hirata M;Kijima Y;Takao S;Okada S;Suzuki M;Imaizumi K;Kawada K;Minami H;Gotoh N;Shimono Y
转移进展仍然是人类乳腺癌死亡的主要原因。具有肿瘤干细胞(CSC)特性的癌细胞驱动远处部位转移的启动和生长。我们之前已经建立了乳腺癌患者来源的肿瘤异种移植(PDX)小鼠模型，在该模型中，CSC标记CD44+的癌细胞在肝脏形成自发的微观转移。在这只PDX小鼠中，转移到肝脏的CD44+癌细胞中S100A10及其家族蛋白的表达水平明显高于原发部位。S100A10在乳腺癌细胞中的敲除抑制和在乳腺癌PDX细胞中的过表达增强了其体外侵袭能力和3D类有机物形成能力。S100A10从机制上调节基质金属蛋白酶活性和干细胞相关基因的表达水平。最后，S100A10的结构性敲除显著降低了它们在体内的肝脏转移能力。这些发现表明，S100A10通过赋予乳腺癌的侵袭能力和CSC特性而发挥乳腺CSCs的转移促进作用。与原发肿瘤干细胞相比，S100蛋白家族成员，包括S100A10，在转移性肿瘤干细胞中高表达。其中，S100A10作为CSC特性和侵袭能力的增强剂，其基因敲除抑制了小鼠异种移植模型中的肝转移。
Metastatic progression remains the major cause of death in human breast cancer. Cancer cells with cancer stem cell (CSC) properties drive initiation and growth of metastases at distant sites. We have previously established the breast cancer patient‐derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, the expression levels of S100A10 and its family proteins were much higher in the CD44+ cancer cells metastasized to the liver than those at the primary site. Knockdown of S100A10 in breast cancer cells suppressed and overexpression of S100A10 in breast cancer PDX cells enhanced their invasion abilities and 3D organoid formation capacities in vitro. Mechanistically, S100A10 regulated the matrix metalloproteinase activity and the expression levels of stem cell–related genes. Finally, constitutive knockdown of S100A10 significantly reduced their metastatic ability to the liver in vivo. These findings suggest that S100A10 functions as a metastasis promoter of breast CSCs by conferring both invasion ability and CSC properties in breast cancers. Members of the S100 protein family, including S100A10, were highly upregulated in metastasized cancer stem cells (CSCs) compared with primary CSCs. Among them, S100A10 functioned as an enhancer of both CSC properties and invasion abilities, and its knockdown suppressed liver metastases in a mouse xenograft model.
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DOI：
10.4137/bcbcr.s25460
发表时间：
2015
期刊：
Breast cancer : basic and clinical research
影响因子：
--
作者：
Jin X;Mu P
通讯作者：
Mu P
DOI：
10.1073/pnas.1006732107
发表时间：
2010-10-19
影响因子：
11.1
作者：
Liu, Huiping;Patel, Manishkumar R.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
3.3
作者：
Boquest, AC;Shahdadfar, A;Brinchmann, JE
通讯作者：
Brinchmann, JE
影响因子：
78.5
作者：
Bresnick, Anne R.;Weber, David J.;Zimmer, Danna B.
通讯作者：
Zimmer, Danna B.
影响因子：
20.3
作者：
O'Connell, Paul A.;Surette, Alexi P.;Waisman, David M.
通讯作者：
Waisman, David M.