Adipocyte-derived exosomes may promote breast cancer progression in type 2 diabetes.
Adipocyte-derived exosomes may promote breast cancer progression in type 2 diabetes.
复制标题
脂肪细胞衍生的外泌体可能会促进2型糖尿病的乳腺癌进展。
DOI：
10.1126/scisignal.abj2807
复制
发表时间：
2021-11-23
影响因子：
7.3
通讯作者：
Denis GV
中科院分区：
文献类型：
--
作者：
Jafari N;Kolla M;Meshulam T;Shafran JS;Qiu Y;Casey AN;Pompa IR;Ennis CS;Mazzeo CS;Rabhi N;Farmer SR;Denis GV
肥胖和代谢性疾病，如胰岛素抵抗和2型糖尿病（T2D），与绝经后妇女的转移性乳腺癌有关。在这里，我们研究了这种联系背后的关键细胞和分子因素。我们发现，原代人脂肪细胞脱落细胞外囊泡，特别是外泌体，诱导表达的基因与上皮间质转化（EMT）和癌干细胞样细胞（CSC）性状在共培养的乳腺癌细胞系。这些基因的转录在暴露于从T2D患者来源的脂肪细胞或胰岛素抗性脂肪细胞脱落的外泌体的细胞中进一步增加，并且在受体细胞中需要表观遗传阅读器蛋白BRD2和BRD4。与癌症相关的血小板反应蛋白家族蛋白TSP5在来自T2D或胰岛素抵抗脂肪细胞的外泌体中更丰富，并部分促成受体细胞中的EMT。乳腺癌患者组织的生物信息学分析显示，COMP（编码TSP5）和BRD 2或BRD 3的更高共表达与较差的预后相关，特别是降低无远处转移生存率。我们的研究结果揭示了代谢异常的脂肪细胞和乳腺癌细胞之间的外泌体介导的串扰机制，这可能会促进T2D患者的肿瘤侵袭性。
Obesity and metabolic diseases, such as insulin resistance and type 2 diabetes (T2D), are associated with metastatic breast cancer in post-menopausal women. Here, we investigated the critical cellular and molecular factors behind this link. We found that primary human adipocytes shed extracellular vesicles—specifically exosomes—that induced the expression of genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem-like cell (CSC) traits in cocultured breast cancer cell lines. Transcription of these genes was further increased in cells exposed to exosomes shed from T2D patient-derived adipocytes or insulin-resistant adipocytes and required the epigenetic reader proteins BRD2 and BRD4 in recipient cells. The thrombospondin family protein TSP5, which is associated with cancer, was more abundant in exosomes from T2D or insulin-resistant adipocytes and partially contributed to EMT in recipient cells. Bioinformatic analysis of breast cancer patient tissue showed that greater co-expression of COMP (which encodes TSP5) and BRD2 or BRD3 correlated with poorer prognosis, specifically decreased distant metastasis-free survival. Our findings reveal a mechanism of exosome-mediated crosstalk between metabolically abnormal adipocytes and breast cancer cells that may promote tumor aggressiveness in T2D patients.
登录
查看更多内容
DOI：
10.1007/s10552-016-0837-z
发表时间：
2017-01
期刊：
Cancer causes & control : CCC
影响因子：
--
作者：
Charlot M;Castro-Webb N;Bethea TN;Bertrand K;Boggs DA;Denis GV;Adams-Campbell LL;Rosenberg L;Palmer JR
通讯作者：
Palmer JR
影响因子：
5.9
作者：
Liu S;Cong Y;Wang D;Sun Y;Deng L;Liu Y;Martin-Trevino R;Shang L;McDermott SP;Landis MD;Hong S;Adams A;D'Angelo R;Ginestier C;Charafe-Jauffret E;Clouthier SG;Birnbaum D;Wong ST;Zhan M;Chang JC;Wicha MS
通讯作者：
Wicha MS
DOI：
10.1158/1078-0432.ccr-15-2239
发表时间：
2016-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Iyengar NM;Zhou XK;Gucalp A;Morris PG;Howe LR;Giri DD;Morrow M;Wang H;Pollak M;Jones LW;Hudis CA;Dannenberg AJ
通讯作者：
Dannenberg AJ
影响因子：
3.8
作者：
Bosco, Jaclyn L. F.;Palmer, Julie R.;Boggs, Deborah A.;Hatch, Elizabeth E.;Rosenberg, Lynn
通讯作者：
Rosenberg, Lynn
DOI：
10.1007/978-3-319-48382-5_13
发表时间：
2017-01-01
期刊：
OBESITY AND LIPOTOXICITY
影响因子：
--
作者：
Engin, Atilla
通讯作者：
Engin, Atilla