BCMA (TNFRSF17) Induces APRIL and BAFF Mediated Breast Cancer Cell Stemness.
BCMA (TNFRSF17) Induces APRIL and BAFF Mediated Breast Cancer Cell Stemness.
复制标题
DOI：
10.3389/fonc.2018.00301
复制
发表时间：
2018
影响因子：
4.7
通讯作者：
Kampa M
中科院分区：
文献类型：
--
作者：
Pelekanou V;Notas G;Athanasouli P;Alexakis K;Kiagiadaki F;Peroulis N;Kalyvianaki K;Kampouri E;Polioudaki H;Theodoropoulos P;Tsapis A;Castanas E;Kampa M
癌症免疫学的最新进展揭示了癌细胞作为新的有希望的治疗靶点的免疫相关特性。两个TNF超家族成员APRIL（TNFSF 13）和BAFF（TNFSF 13 B）是II型膜蛋白，通过蛋白水解裂解以活性形式释放，主要参与B淋巴细胞成熟，也与几种实体瘤（包括乳腺癌）中的肿瘤生长和侵袭性相关。在目前的工作中，我们研究了APRIL和BAFF对乳腺癌细胞上皮间质转化、迁移和干细胞的影响。我们的研究结果表明，这两种分子通过增加ALDH 1A 1，KLF 4和NANOG等多能性基因的表达来增加乳腺癌细胞的上皮向间质转化和迁移能力，以及癌症干细胞数量。这些作用由它们的共同受体BCMA（TNFRSF 17）和JNK信号通路介导。有趣的是，来自乳腺癌细胞和患者的转录数据分析显示，雄激素可以增加APRIL转录，随后以自分泌/旁分泌方式增强其多能性效应。总之，我们的数据表明APRIL和BAFF在乳腺癌疾病进展中的可能作用，并为治疗抗性的新可能机制提供了证据，这可能与芳香化酶底物治疗的患者特别相关，局部雄激素增加。
Recent advances in cancer immunology revealed immune-related properties of cancer cells as novel promising therapeutic targets. The two TNF superfamily members, APRIL (TNFSF13), and BAFF (TNFSF13B), which are type II membrane proteins, released in active forms by proteolytic cleavage and are primarily involved in B-lymphocyte maturation, have also been associated with tumor growth and aggressiveness in several solid tumors, including breast cancer. In the present work we studied the effect of APRIL and BAFF on epithelial to mesenchymal transition, migration, and stemness of breast cancer cells. Our findings show that both molecules increase epithelial to mesenchymal transition and migratory capacity of breast cancer cells, as well as cancer stem cell numbers, by increasing the expression of pluripotency genes such as ALDH1A1, KLF4, and NANOG. These effects are mediated by their common receptor BCMA (TNFRSF17) and the JNK signaling pathway. Interestingly, transcriptional data analysis from breast cancer cells and patients revealed that androgens can increase APRIL transcription and subsequently, in an autocrine/paracrine manner, enhance its pluripotency effect. In conclusion, our data suggest a possible role of APRIL and BAFF in breast cancer disease progression and provide evidence for a new possible mechanism of therapy resistance, that could be particularly relevant in aromatase inhibitors-treated patients, were local androgen is increased.
登录
查看更多内容
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
4.7
作者：
Garcia-Castro, Araceli;Zonca, Manuela;Planelles, Lourdes
通讯作者：
Planelles, Lourdes
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
28.2
作者：
Brooks MD;Wicha MS
通讯作者：
Wicha MS
影响因子：
17.1
作者：
Giltnane JM;Hutchinson KE;Stricker TP;Formisano L;Young CD;Estrada MV;Nixon MJ;Du L;Sanchez V;Ericsson PG;Kuba MG;Sanders ME;Mu XJ;Van Allen EM;Wagle N;Mayer IA;Abramson V;Gόmez H;Rizzo M;Toy W;Chandarlapaty S;Mayer EL;Christiansen J;Murphy D;Fitzgerald K;Wang K;Ross JS;Miller VA;Stephens PJ;Yelensky R;Garraway L;Shyr Y;Meszoely I;Balko JM;Arteaga CL
通讯作者：
Arteaga CL