RANK蛋白促進(jìn)人乳腺癌的啟動、進(jìn)展和轉(zhuǎn)移,，相關(guān)研究論文發(fā)表在Cancer Research雜志上,，表明抑制這種受體可能對乳腺腫瘤的治療有效果。
Bellvitge生物醫(yī)學(xué)研究所（IDIBELL）的研究表明,，RANK信號轉(zhuǎn)導(dǎo)通路的過度激活通過促進(jìn)乳腺細(xì)胞分化成腫瘤干細(xì)胞,，使得人類乳腺上皮細(xì)胞轉(zhuǎn)移的啟動、進(jìn)展和轉(zhuǎn)移,。
RANK信號通路
這項研究是由Bellvitge生物醫(yī)學(xué)研究所（IDIBELL）Eva Gonzalez-Suarez領(lǐng)導(dǎo),。一年前，研究小組發(fā)表的一項研究論文證實這條信號途徑在小鼠模型中乳腺腫瘤有關(guān),。我們看到,，當(dāng)這條途徑是過度活躍的時候，動物更容易患上乳腺癌,，當(dāng)藥物抑制這條信號途徑時腫瘤減少,。
這項研究的出發(fā)點是觀察人身上RANK過度表達(dá)的影響。首先研究人員用健康的乳腺上皮細(xì)胞株,，發(fā)現(xiàn)RANK受體的過度表達(dá)誘導(dǎo)干細(xì)胞和上皮間質(zhì)轉(zhuǎn)化到成具有惡性腫瘤特征的細(xì)胞,，但并不發(fā)展成腫瘤
下一步是觀察蛋白質(zhì)在乳腺腫瘤細(xì)胞的過度表達(dá)的影響。我們看到它在腫瘤干細(xì)胞中是如何的生成增加的,，當(dāng)我們將RANK注入了動物模型中時,，腫瘤發(fā)生和轉(zhuǎn)移會增加。
最后,，研究人員使用乳腺癌的臨床標(biāo)本,。高水平RANK的腫瘤細(xì)胞擴散和轉(zhuǎn)移等級也較高。這意味著高水平蛋白質(zhì)與腫瘤預(yù)后不良相關(guān),。因此,，本研究證實人體細(xì)胞中，RANK可能會增加乳腺癌啟動,、進(jìn)展及轉(zhuǎn)移,。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-12-0044
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PMID:
RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis
Marta Palafox, Irene Ferrer, Pasquale Pellegrini, Sergi Vila, Sara Hernandez-Ortega, Ander Urruticoechea, Fina Climent, et al.
Paracrine signaling through RANK pathway mediates the expansion of mammary epithelia that occurs during pregnancy and activation of RANK pathway promotes mammary tumorigenesis in mice. In this study we extend these previous data to human cells and demonstrate that the RANK pathway promotes the development of mammary stem cells and breast cancer. Overexpression of RANK (FL-RANK) in a panel of tumoral and normal human mammary cells induces the expression of breast cancer stem and basal/stem cell markers. High levels of RANK in untransformed MCF10A cells induce changes associated with both stemness and transformation including mammary gland reconstitution, epithelial-mesenchymal transition, increased migration and anchorage independent growth. In addition, spheroids of RANK-overexpressing MCF10A cells displayed disrupted acinar formation, impaired growth arrest and polarization, and luminal filling. RANK overexpression in tumor cells with non functional BRCA1, enhances invasiveness in acinar cultures and increases tumorigenesis and metastasis in immunodeficient mice. High levels of RANK were found in human primary breast adenocarcinomas that lack expression of the hormone receptors, estrogen and progesterone, and in tumors with high pathological grade and proliferation index; high RANK/RANKL expression was significantly associated with metastatic tumors. Together, our findings demonstrate that RANK promotes tumor initiation, progression and metastasis in human mammary epithelial cells by increasing the population of CD44+CD24- cells, inducing stemness and epithelial mesenchymal transition. These results suggest that RANK expression in primary breast cancer associates with poor prognosis.
