TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway.
TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway.
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TAGLN 通过 RhoA/ROCK 通路介导硬度调节的卵巢癌进展
DOI：
10.1186/s13046-021-02091-6
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发表时间：
2021-09-19
期刊：
影响因子：
--
通讯作者：
Gao Q
中科院分区：
文献类型：
--
作者：
Wei X;Lou H;Zhou D;Jia Y;Li H;Huang Q;Ma J;Yang Z;Sun C;Meng Y;Xu S;Yang X;Li X;Ji T;Guo Z;Gao Q
卵巢癌(OC)的进展是一个尚未满足的医学挑战。由于在上皮性卵巢癌(EOC)患者的细胞减灭术中，大网膜转移灶比其原发灶更难触及，因此我们从生物力学的角度来研究OC的进展。用原子力显微镜(AFM)测量组织的杨氏模数。制备了胶原包被的聚丙烯酰胺水凝胶(PA Gel)体系，以模拟体外的软、硬基质。用Transwell实验、免疫荧光、免疫印迹和免疫组织化学等方法对TAGLN的体内外作用进行评价。我们定量地证实，与配对的原发肿瘤相比，大网膜转移瘤在结缔组织发育中更坚硬和更丰富，并进一步证明基质僵硬可以显著调节OC的进展。值得注意的是，编码肌动蛋白交联/凝胶蛋白的TAGLN基因被鉴定为一个有效的机械敏感基因，它可以通过调节RhoA/ROCK通路，与Src的激活反应形成一个调控环，从而调节僵硬调节的OC进程。这些数据表明，靶向细胞外基质(ECM)僵硬可能会阻碍OC的进展，值得注意的是，靶向TAGLN可能为OC治疗提供有前景的临床治疗价值。网上版载有补充材料，可在10.1186/s13046-021-02091-6查阅。
Ovarian cancer (OC) progression is an unmet medical challenge. Since omental metastases were palpated harder than their primary counterparts during cytoreductive surgery of patients with epithelial ovarian cancer (EOC), we were inspired to investigate OC progression from the perspective of biomechanics. Atomic Force Microscope (AFM) was used to measure the Young’s modulus of tissues. The collagen-coated polyacrylamide hydrogel (PA gel) system was prepared to mimic the soft and stiff substrates in vitro. The effect of TAGLN was evaluated both in vitro and in vivo using transwell assay, immunofluorescence, western blot analysis and immunohistochemistry. We quantitatively confirmed that omental metastases were stiffer and more abundant in desmoplasia compared with paired primary tumors, and further demonstrated that matrix stiffness could notably regulate OC progression. Remarkably, TAGLN, encoding an actin cross-linking/gelling protein, was identified as a potent mechanosensitive gene that could form a regulation loop with Src activation reacting to environmental stiffness, thus mediating stiffness-regulated OC progression through regulating RhoA/ROCK pathway. These data demonstrate that targeting extra-cellular matrix (ECM) stiffness could probably hamper OC progression, and of note, targeting TAGLN might provide promising clinical therapeutic value for OC therapy. The online version contains supplementary material available at 10.1186/s13046-021-02091-6.
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影响因子：
21.3
作者：
Miroshnikova YA;Mouw JK;Barnes JM;Pickup MW;Lakins JN;Kim Y;Lobo K;Persson AI;Reis GF;McKnight TR;Holland EC;Phillips JJ;Weaver VM
通讯作者：
Weaver VM
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0711704105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Na, Sungsoo;Collin, Olivier;Wang, Ning
通讯作者：
Wang, Ning
DOI：
10.1039/c5ib00040h
发表时间：
2015-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Acerbi I;Cassereau L;Dean I;Shi Q;Au A;Park C;Chen YY;Liphardt J;Hwang ES;Weaver VM
通讯作者：
Weaver VM
影响因子：
4
作者：
Feng J;Gou J;Jia J;Yi T;Cui T;Li Z
通讯作者：
Li Z