Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma.
Hyaluronic acid enhances cell migration and invasion via the YAP1/TAZ-RHAMM axis in malignant pleural mesothelioma.
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DOI：
10.18632/oncotarget.20750
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发表时间：
2017-11-07
期刊：
影响因子：
--
通讯作者：
Maesawa C
中科院分区：
文献类型：
--
作者：
Shigeeda W;Shibazaki M;Yasuhira S;Masuda T;Tanita T;Kaneko Y;Sato T;Sekido Y;Maesawa C
大多数恶性间皮瘤(MPM)通常表现为激活形式的YAP1和转录共激活因子与PDZ结合基序(TAZ)，它在转录上调节透明质酸介导的运动受体(RAMM)。由于RHAMM参与了多种肿瘤的细胞迁移和侵袭，我们推测胸液中的透明质酸(HA)可能通过通过RHAMM刺激细胞的迁移和侵袭而影响间皮瘤的进展。YAP1/TAZ基因敲除后RHAMM的表达水平降低，而激活形式YAP1的表达增强，提示RHAMM在MPM细胞中受YAP1/TAZ调控。YAP1/TAZ或RHAMM基因敲除后，细胞的迁移和侵袭能力也降低。值得注意的是，HA处理增加了细胞的运动性和侵袭性，这一点被rhamm基因敲除后被取消，这表明HA可能通过rhamm促进MPM细胞的局部进展。此外，氟伐他汀通过调节YAP1/TAZ活性来调节RHAMM转录，降低了MPM细胞的运动性和侵袭性。综上所述，这些数据表明，HA是一个“不利的”因素，因为它促进间皮瘤的恶性，YAP1/TAZ-rhamm轴可能有潜在的治疗价值，以抑制MPM的疾病进展。
Most malignant mesotheliomas (MPMs) frequently show activated forms of Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which transcriptionally regulates the receptor for hyaluronic acid-mediated motility (RHAMM). As RHAMM is involved in cell migration and invasion in various tumors, we speculated that hyaluronic acid (HA) in pleural fluid might affect the progression of mesothelioma by stimulating cell migration and invasion through RHAMM. The level of RHAMM expression was decreased by YAP1/TAZ knockdown, and conversely increased by forced expression of the active form of YAP1, suggesting that RHAMM was regulated by YAP1/TAZ in MPM cells. Cell migration and invasion were also decreased by YAP1/TAZ or RHAMM knockdown. Notably, HA treatment increased cell motility and invasion, and this was abolished by RHAMM knockdown, suggesting that HA may augment local progression of MPM cells via RHAMM. Furthermore, treatment with fluvastatin, which regulates RHAMM transcription by modulating YAP1/TAZ activity, decreased the motility and invasion of MPM cells. Collectively, these data suggest that HA is an “unfavorable” factor because it promotes malignancy in mesothelioma and that the YAP1/TAZ-RHAMM axis may have potential value as a therapeutic target for inhibition of disease progression in MPM.
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影响因子：
8
作者：
Ehsanian, R.;Brown, M.;Lu, H.;Yang, X. P.;Pattatheyil, A.;Yan, B.;Duggal, P.;Chuang, R.;Doondeea, J.;Feller, S.;Sudol, M.;Chen, Z.;Van Waes, C.
通讯作者：
Van Waes, C.
影响因子：
8.8
作者：
Schmaus, A.;Klusmeier, S.;Rothley, M.;Dimmler, A.;Sipos, B.;Faller, G.;Thiele, W.;Allgayer, H.;Hohenberger, P.;Post, S.;Sleeman, J. P.
通讯作者：
Sleeman, J. P.
DOI：
10.1016/j.jtho.2016.04.028
发表时间：
2016-08
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Carbone M;Kanodia S;Chao A;Miller A;Wali A;Weissman D;Adjei A;Baumann F;Boffetta P;Buck B;de Perrot M;Dogan AU;Gavett S;Gualtieri A;Hassan R;Hesdorffer M;Hirsch FR;Larson D;Mao W;Masten S;Pass HI;Peto J;Pira E;Steele I;Tsao A;Woodard GA;Yang H;Malik S
通讯作者：
Malik S
影响因子：
7.3
作者：
Misra S;Hascall VC;Markwald RR;Ghatak S
通讯作者：
Ghatak S
TAZ 促进细胞增殖和上皮间质转化，并受 hippo 通路抑制
影响因子：
5.3
作者：
Lei, Qun-Ying;Zhang, Heng;Guan, Kun-Liang
通讯作者：
Guan, Kun-Liang