细胞主要通过调节肌动蛋白细胞骨架来感知和响应来自细胞外基质的各种机械力。机械力可以通过称为机械转导的过程转化为生化信号。 Yes相关蛋白（YAP）是Hippo信号传导的效应子和机械转导的介质，但机械力如何调节Hippo信号传导仍然是一个悬而未决的问题。我们提出视黄酸诱导蛋白 14 (RAI14) 对机械力做出反应并调节 Hippo 信号传导。 RAI14 正向调节 YAP 的活性。 RAI14 与 Hippo 通路的关键组成部分 NF2 相互作用，并且相互作用发生在丝状肌动蛋白上。当细胞内的机械力保持较低水平时，NF2 与 RAI14 和丝状肌动蛋白分离，导致与 LATS1 的相互作用增加并激活 Hippo 通路。临床数据表明，肿瘤组织中的组织硬度以及 RAI14 和 YAP 的表达上调，并且 RAI14 与胃癌患者的不良结局密切相关。我们的数据表明，RAI14 将机械转导与 Hippo 信号传导联系起来，并介导 Hippo 相关的生物功能，例如癌症进展。© 2024。作者。

Cells sense and respond to various mechanical forces from the extracellular matrix primarily by modulating the actin cytoskeleton. Mechanical forces can be translated into biochemical signals in a process called mechanotransduction. Yes-associated protein (YAP) is an effector of Hippo signaling and a mediator of mechanotransduction, but how mechanical forces regulate Hippo signaling is still an open question. We propose that retinoic acid-induced protein 14 (RAI14) responds to mechanical forces and regulates Hippo signaling. RAI14 positively regulates the activity of YAP. RAI14 interacts with NF2, a key component of the Hippo pathway, and the interaction occurs on filamentous actin. When mechanical forces are kept low in cells, NF2 dissociates from RAI14 and filamentous actin, resulting in increased interactions with LATS1 and activation of the Hippo pathway. Clinical data show that tissue stiffness and expression of RAI14 and YAP are upregulated in tumor tissues and that RAI14 is strongly associated with adverse outcome in patients with gastric cancer. Our data suggest that RAI14 links mechanotransduction with Hippo signaling and mediates Hippo-related biological functions such as cancer progression.© 2024. The Author(s).