The role of lipolysis stimulated lipoprotein receptor in breast cancer and directing breast cancer cell behavior.
The role of lipolysis stimulated lipoprotein receptor in breast cancer and directing breast cancer cell behavior.
复制标题
DOI：
10.1371/journal.pone.0091747
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fleming JM
中科院分区：
文献类型：
--
作者：
Reaves DK;Fagan-Solis KD;Dunphy K;Oliver SD;Scott DW;Fleming JM
乳腺癌的密蛋白低分子亚型在临床上特别受关注，这些肿瘤中的大多数是预后不良、三阴性、浸润性导管癌。密蛋白低肿瘤的特点是癌症干细胞样特征以及细胞连接和粘附蛋白的低表达。在此，我们试图确定脂解刺激脂蛋白受体 (LSR) 在乳腺癌和癌细胞行为中的作用，因为 LSR 最近与肿瘤起始特征相关。我们发现，LSR 在健康乳腺组织内的上皮细胞、内皮细胞和基质细胞以及肿瘤上皮细胞中表达。在原发性乳腺肿瘤活检中，与浸润性小叶癌相比，LSR 表达与浸润性导管癌以及 ERα 阳性肿瘤和乳腺癌细胞系显着相关。在紧密蛋白低的乳腺癌细胞系中，LSR 水平显着降低，功能研究表明，将 LSR 重新引入紧密蛋白低的细胞系中，可以抑制 EMT 表型并减少个体细胞迁移。然而，我们的数据表明LSR可能促进集体细胞迁移。在claudin-low乳腺癌细胞系中重新引入LSR可重建紧密连接蛋白表达并与跨上皮电阻相关，从而将claudin-low细胞系恢复为其他内在分子亚型。此外，LSR的过度表达改变了参与转化和肿瘤发生的途径的基因表达，并增强了锚定独立条件下的增殖和存活，这凸显了LSR信号的重建促进了侵袭/肿瘤起始细胞行为。总的来说，这些数据强调了 LSR 在推动侵袭性乳腺癌行为中的直接作用。
The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by cancer stem cell-like features and low expression of cell junction and adhesion proteins. Herein, we sought to define the role of lipolysis stimulated lipoprotein receptor (LSR) in breast cancer and cancer cell behavior as LSR was recently correlated with tumor-initiating features. We show that LSR was expressed in epithelium, endothelium, and stromal cells within the healthy breast tissue, as well as in tumor epithelium. In primary breast tumor bioposies, LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, as well as ERα positive tumors and breast cancer cell lines. LSR levels were significantly reduced in claudin-low breast cancer cell lines and functional studies illustrated that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may promote collective cell migration. Re-introduction of LSR in claudin-low breast cancer cell lines reestablished tight junction protein expression and correlated with transepithelial electrical resistance, thereby reverting claudin-low lines to other intrinsic molecular subtypes. Moreover, overexpression of LSR altered gene expression of pathways involved in transformation and tumorigenesis as well as enhanced proliferation and survival in anchorage independent conditions, highlighting that reestablishment of LSR signaling promotes aggressive/tumor initiating cell behaviors. Collectively, these data highlight a direct role for LSR in driving aggressive breast cancer behavior.
登录
查看更多内容
影响因子：
5.4
作者：
Ahmad, Nazir;Girardet, Jean-Michel;Corbier, Catherine
通讯作者：
Corbier, Catherine
影响因子：
4.9
作者：
Neal-Perry, Genevieve;Nejat, Edward;Dicken, Cary
通讯作者：
Dicken, Cary
影响因子：
7.4
作者：
Allred, DC;Brown, P;Medina, D
通讯作者：
Medina, D
影响因子：
3.7
作者：
Delort L;Lequeux C;Dubois V;Dubouloz A;Billard H;Mojallal A;Damour O;Vasson MP;Caldefie-Chézet F
通讯作者：
Caldefie-Chézet F
DOI：
10.1186/bcr3215
发表时间：
2012-06-25
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fleming JM;Miller TC;Kidacki M;Ginsburg E;Stuelten CH;Stewart DA;Troester MA;Vonderhaar BK
通讯作者：
Vonderhaar BK