Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation.
Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation.
复制标题
甲状旁腺激素样激素是头颈癌的不良预后标志物，并通过RUNX2调节促进细胞生长。
DOI：
10.1038/srep41131
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发表时间：
2017-01-25
影响因子：
4.6
通讯作者：
Shiah SG
中科院分区：
文献类型：
--
作者：
Chang WM;Lin YF;Su CY;Peng HY;Chang YC;Hsiao JR;Chen CL;Chang JY;Shieh YS;Hsiao M;Shiah SG
甲状旁腺激素样激素(PTHLH)是一种自分泌/旁分泌配体，在头颈部鳞状细胞癌中表达上调。然而，HNSCC的细胞功能和调控机制仍不清楚。我们探讨了甲状旁腺激素释放激素在HNSCC患者中的临床意义，并验证了RUNX2/PTHLH轴在促进HNSCC细胞生长中的作用。在患者中，甲状旁腺素是一个预后不良的标志物。在NOD-SCID小鼠中，PTHLH的表达通过自分泌/旁分泌作用增加细胞的增殖能力，并升高血钙水平。在公开的HNSCC微阵列队列中，发现PTH1H与RUNX2共表达。生理上，PTHLH受RUNX2调控，也是关键的钙调节因子。然而，钙离子浓度的升高也增加了RUNX2的表达。甲状旁腺素、钙和RUNX2在HNSCC中形成正反馈环路。此外，异位表达RUNX2还通过增加PTHLH的表达促进细胞增殖。通过基因芯片分析发现，甲状旁腺激素能刺激HNSCC细胞中细胞周期调节因子CcNA2、CCNE2和CDC25A的表达，并且这些基因在HNSCC患者中也表达上调。综上所述，我们的研究结果表明，PTHLH的表达是HNSCC患者预后较差的指标，RUNX2-PTHLH轴参与了HNSCC的生长。
Parathyroid Hormone-Like Hormone (PTHLH) is an autocrine/paracrine ligand that is up-regulated in head and neck squamous cell carcinoma (HNSCC). However, the cellular function and regulatory mechanism in HNSCC remains obscure. We investigated the clinical significance of PTHLH in HNSCC patients, and verified the role of RUNX2/PTHLH axis, which is stimulated HNSCC cell growth. In patients, PTHLH is a poor prognosis marker. PTHLH expression lead to increasing the cell proliferation potential through an autocrine/paracrine role and elevating blood calcium level in Nod-SCID mice. In public HNSCC microarray cohorts, PTHLH is found to be co-expressed with RUNX2. Physiologically, PTHLH is regulated by RUNX2 and also acting as key calcium regulator. However, elevations of calcium concentration also increased the RUNX2 expression. PTHLH, calcium, and RUNX2 form a positive feedback loop in HNSCC. Furthermore, ectopic RUNX2 expression also increased PTHLH expression and promoted proliferation potential through PTHLH expression. Using cDNA microarray analysis, we found PTHLH also stimulated expression of cell cycle regulators, namely CCNA2, CCNE2, and CDC25A in HNSCC cells, and these genes are also up-regulated in HNSCC patients. In summary, our results reveal that PTHLH expression is a poor prognosis marker in HNSCC patients, and RUNX2-PTHLH axis contributes to HNSCC tumor growth.