TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway

Autor: Xiao Wei, Hua Lou, Dongchen Zhou, Yijuan Jia, Huayi Li, Quanfu Huang, Jingjing Ma, Zongyuan Yang, Chaoyang Sun, Yunchong Meng, Sen Xu, Xin Yang, Xiaoting Li, Teng Ji, Zhongzhen Guo, Qinglei Gao
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-14 (2021)
Druh dokumentu: article
ISSN: 1756-9966
DOI: 10.1186/s13046-021-02091-6
Popis: Abstract Background 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. Methods 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. Results 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. Conclusions 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.
Databáze: Directory of Open Access Journals
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