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Hyaluronan Degradation Promotes Cancer via Hippo-YAP Signaling: An Intervention Point for Cancer Therapy.
BioEssays ( IF 4 ) Pub Date : 2020-05-25 , DOI: 10.1002/bies.202000005
Takuya Ooki 1 , Masanori Hatakeyama 1
Affiliation  

High‐molecular‐weight hyaluronan acts as a ligand of the tumor‐suppressive Hippo signal, whereas degradation of hyaluronan from a high‐molecular‐weight form to a low‐molecular‐weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro‐oncogenic transcriptional coactivator yes‐associated protein (YAP), which creates a cancer‐predisposing microenvironment and drives neoplastic transformation of cells through both cell‐autonomous and non‐cell‐autonomous mechanisms. In fact, accumulation of low‐molecular‐weight hyaluronan in tissue stroma is observed in many types of cancers. Since inhibition of YAP activity suppresses tumor growth in vivo, pharmacological intervention of the Hippo‐YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo‐YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors.

中文翻译:

透明质酸降解通过 Hippo-YAP 信号传导促进癌症:癌症治疗的干预点。

高分子量透明质酸作为抑制肿瘤的 Hippo 信号的配体,而透明质酸酶 2 将透明质酸从高分子量形式降解为低分子量形式会抑制 Hippo 信号激活,从而激活原-致癌转录共激活因子是相关蛋白(YAP),它创造了一个易患癌症的微环境,并通过细胞自主和非细胞自主机制驱动细胞的肿瘤转化。事实上,在许多类型的癌症中都观察到低分子量透明质酸在组织基质中的积累。由于抑制 YAP 活性可抑制体内肿瘤生长,因此对 Hippo-YAP 信号的药理学干预是未来药物开发的一种有吸引力的方法。在这次审查中,还讨论了作为抑制 Hippo-YAP 信号的新方法的过度透明质酸降解的药理学干预。透明质酸酶抑制剂的开发可能为人类恶性肿瘤提供新的治疗策略。
更新日期:2020-06-29
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