RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis.
RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis.
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DOI：
10.1016/j.stemcr.2017.06.002
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发表时间：
2017-08-08
影响因子：
5.9
通讯作者：
Noy N
中科院分区：
文献类型：
--
作者：
Karunanithi S;Levi L;DeVecchio J;Karagkounis G;Reizes O;Lathia JD;Kalady MF;Noy N
跨膜蛋白STRA 6在被维生素A结合的血清视黄醇结合蛋白4（RBP 4）激活时充当维生素A转运蛋白和细胞因子受体。在结肠癌的异种移植小鼠模型中，STRA 6活化转导JAK 2-STAT 3信号级联并促进肿瘤发生。我们发现RBP 4和STRA 6表达与肿瘤预后不良相关。下调结肠癌细胞中的STRA 6或RBP 4降低了癌症干细胞的分数及其球体和肿瘤起始频率。此外，我们表明，高脂饮食（HFD）增加LGR 5的表达和促进肿瘤生长的异种移植模型独立的肥胖。HFD增加了STRA 6水平，并且STRA 6的下调延迟并损害肿瘤起始、肿瘤生长和干性标志物的表达。总之，这些数据证明了STRA 6和RBP 4在维持结肠癌自我更新中的关键作用，并且该途径是消耗HFD有助于结肠癌发生的重要环节。STRA 6和RBP 4表达与结直肠癌预后不良相关STRA 6和RBP 4对维持结肠癌干细胞至关重要RBP 4-STRA 6通路连接高脂饮食喂养和结肠癌发生Karunanithi及其同事证明RBP 4-STRA 6通路对结肠癌干细胞（CSC）维持至关重要。下调结肠癌细胞中的STRA 6或RBP 4会减少CSC群体和自我更新。响应于高脂肪喂养的CSC标志物和肿瘤生长水平的增加在STRA 6沉默后被消除。RBP 4-STRA 6通路可能在高脂肪喂养和结肠癌发生之间提供联系。
The transmembrane protein, STRA6, functions as a vitamin A transporter and a cytokine receptor when activated by vitamin A-bound serum retinol binding protein 4 (RBP4). STRA6 activation transduces a JAK2-STAT3 signaling cascade and promotes tumorigenesis in a xenograft mouse model of colon cancer. We show here that RBP4 and STRA6 expression is associated with poor oncologic prognosis. Downregulating STRA6 or RBP4 in colon cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency. Furthermore, we show that high-fat diet (HFD) increases LGR5 expression and promotes tumor growth in a xenograft model independent of obesity. HFD increased STRA6 levels, and downregulation of STRA6 delays and impairs tumor initiation, tumor growth, and expression of stemness markers. Together, these data demonstrate a key role of STRA6 and RBP4 in the maintenance of colon cancer self-renewal and that this pathway is an important link through which consumption of HFD contributes to colon carcinogenesis. STRA6 and RBP4 expression is associated with poor colorectal cancer prognosis STRA6 and RBP4 are critical for maintenance of colon cancer stem cells RBP4-STRA6 pathway links high-fat diet feeding and colon carcinogenesis Karunanithi and colleagues demonstrate that the RBP4-STRA6 pathway is critical for colon cancer stem cell (CSC) maintenance. Downregulating STRA6 or RBP4 in colon cancer cells decreases CSC population and self-renewal. Increased levels of CSC markers and tumor growth in response to high-fat feeding are abrogated upon STRA6 silencing. The RBP4-STRA6 pathway may provide a link between high-fat feeding and colon carcinogenesis.
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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
DOI：
10.1126/science.aad8266
发表时间：
2016-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen Y;Clarke OB;Kim J;Stowe S;Kim YK;Assur Z;Cavalier M;Godoy-Ruiz R;von Alpen DC;Manzini C;Blaner WS;Frank J;Quadro L;Weber DJ;Shapiro L;Hendrickson WA;Mancia F
通讯作者：
Mancia F
影响因子：
8.2
作者：
Montgomery, M. K.;Hallahan, N. L.;Turner, N.
通讯作者：
Turner, N.
影响因子：
0.1
作者：
Hogan, J.;Dejulius, K.;Kalady, M. F.
通讯作者：
Kalady, M. F.
DOI：
10.1084/jem.20131195
发表时间：
2013-12-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lotti F;Jarrar AM;Pai RK;Hitomi M;Lathia J;Mace A;Gantt GA Jr;Sukhdeo K;DeVecchio J;Vasanji A;Leahy P;Hjelmeland AB;Kalady MF;Rich JN
通讯作者：
Rich JN