Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals.
Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals.
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DOI：
10.1038/s41598-020-77639-1
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发表时间：
2020-11-25
影响因子：
4.6
通讯作者：
Van de Walle GR
中科院分区：
文献类型：
--
作者：
Ledet MM;Harman RM;Fan JC;Schmitt-Matzen E;Diaz-Rubio ME;Zhang S;Van de Walle GR
确定自然保护物种免受癌症发展的机制对于预防和治疗癌症至关重要。在这里，我们描述了一种新的癌症抑制机制，通过乳腺细胞分泌的生物活性因子，这是目前在驯养的哺乳动物与乳腺癌发病率低。具体而言，这些生物活性因子在体外诱导三阴性乳腺癌细胞（TNBC）死亡，并在体内异种移植TNBC小鼠模型中降低致瘤性。RNA深度测序显示，在分泌组培养的TNBC细胞中，与乳腺癌进展相关的基因显著下调。进一步深入的多组学分析将鞘磷脂确定为关键分泌因子，并且通过抑制鞘磷脂信号通路证实了它们的作用。我们推测，分泌的鞘磷脂在哺乳动物的乳腺癌的自然发病率低介导的消除癌细胞。这项研究有助于在抗癌物种中发现越来越多的保护机制。
Determining mechanisms that naturally protect species from developing cancer is critical in order to prevent and treat cancer. Here, we describe a novel cancer-suppressing mechanism, via the secretion of bioactive factors by mammary cells, that is present in domesticated mammals with a low mammary cancer incidence. Specifically, these bioactive factors induced triple-negative breast cancer cell (TNBC) death in vitro and reduced tumorigenicity in a xenograft TNBC mouse model in vivo. RNA deep sequencing showed significant downregulation of genes associated with breast cancer progression in secretome-cultured TNBC cells. Further in-depth multi-omics analysis identified sphingomyelins as key secreted factors, and their role was confirmed via inhibition of the sphingomyelin signaling pathway. We speculate that secreted sphingomyelins in the mammary gland of mammals with a naturally low incidence of mammary cancer mediate the elimination of cancer cells. This study contributes to the growing list of protective mechanisms identified in cancer-proof species.
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哺乳动物最大寿命的脂质组决定因素
影响因子：
4.6
作者：
Bozek K;Khrameeva EE;Reznick J;Omerbašić D;Bennett NC;Lewin GR;Azpurua J;Gorbunova V;Seluanov A;Regnard P;Wanert F;Marchal J;Pifferi F;Aujard F;Liu Z;Shi P;Pääbo S;Schroeder F;Willmitzer L;Giavalisco P;Khaitovich P
通讯作者：
Khaitovich P
影响因子：
29
作者：
Ma S;Yim SH;Lee SG;Kim EB;Lee SR;Chang KT;Buffenstein R;Lewis KN;Park TJ;Miller RA;Clish CB;Gladyshev VN
通讯作者：
Gladyshev VN
影响因子：
7.3
作者：
Ma S;Gladyshev VN
通讯作者：
Gladyshev VN
影响因子：
7.4
作者：
Bird, Susan S.;Marur, Vasant R.;Sniatynski, Matthew J.;Greenberg, Heather K.;Kristal, Bruce S.
通讯作者：
Kristal, Bruce S.
AHNAK 通过靶向三阴性乳腺癌的多种途径抑制肿瘤增殖和侵袭
DOI：
10.1186/s13046-017-0522-4
发表时间：
2017-05-12
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Chen B;Wang J;Dai D;Zhou Q;Guo X;Tian Z;Huang X;Yang L;Tang H;Xie X
通讯作者：
Xie X