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Shear stress triggered circular dorsal ruffles formation to facilitate cancer cell migration
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2021-06-22 , DOI: 10.1016/j.abb.2021.108967 Xiang Qin 1 , Yuehui Zhang 1 , Yuchen He 1 , Kang Chen 1 , Yixi Zhang 1 , Ping Li 1 , Ying Jiang 1 , Shun Li 1 , Tingting Li 1 , Hong Yang 1 , Chunhui Wu 1 , Chuan Zheng 2 , Jie Zhu 2 , Fengming You 2 , Yiyao Liu 3
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2021-06-22 , DOI: 10.1016/j.abb.2021.108967 Xiang Qin 1 , Yuehui Zhang 1 , Yuchen He 1 , Kang Chen 1 , Yixi Zhang 1 , Ping Li 1 , Ying Jiang 1 , Shun Li 1 , Tingting Li 1 , Hong Yang 1 , Chunhui Wu 1 , Chuan Zheng 2 , Jie Zhu 2 , Fengming You 2 , Yiyao Liu 3
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Circular dorsal ruffles (CDRs) are a kind of special ring-shaped membrane structure rich in F-actin, it is highly involved in the invasion-metastasis of tumor. Shear stress is one of the biophysical elements that affects the fate of tumor cells. However, how shear stress contributes to the CDRs formation is still unclear. In this study, we found that shear stress stimulated the formation of CDRs and promoted the migration of human breast MDA-MB-231 carcinoma cells. Integrin-linked kinase (ILK) mediated the recruiting of ADP-ribosylation factors (ARAP1/Arf1) to CDRs. Meanwhile, the transfection of ARAP1 or Arf1 mutant decreased the number of cells with CDRs, the CDRs areas and perimeters, thus blocked the cancer cell migration. This indicated that the ARAP1/Arf1 were necessary for the CDRs formation and cancer cell migration. Further study revealed that shear stress could stimulate the formation of intracellular macropinocytosis (MPS) thus promoted the ARAP1/Arf1 transportation to early endosome to regulate cancer cell migration after the depolymerization of CDRs. Our study elucidates that the CDRs formation is essential in shear stress-induced breast cancer cell migration, which provides a new research target for exploring the cytoskeletal mechanisms of breast cancer malignance.
中文翻译：
剪切应力引发圆形背侧褶边形成，促进癌细胞迁移
圆形背侧皱褶（CDRs）是一种富含F-肌动蛋白的特殊环状膜结构，与肿瘤的侵袭转移密切相关。剪切应力是影响肿瘤细胞命运的生物物理因素之一。然而，剪切应力如何促进 CDR 的形成仍不清楚。在这项研究中，我们发现剪切应力刺激CDR的形成并促进人乳腺MDA-MB-231癌细胞的迁移。整合素连接激酶 (ILK) 介导 ADP-核糖基化因子 (ARAP1/Arf1) 向 CDR 的募集。同时，转染ARAP1或Arf1突变体可以减少带有CDR的细胞数量、CDR面积和周长，从而阻断癌细胞的迁移。这表明ARAP1/Arf1对于CDR的形成和癌细胞迁移是必需的。进一步研究发现，剪切应力可以刺激细胞内巨胞饮作用（MPS）的形成，从而促进ARAP1/Arf1转运至早期内体，从而在CDR解聚后调节癌细胞迁移。我们的研究阐明了CDR的形成对于剪切应力诱导的乳腺癌细胞迁移至关重要，这为探索乳腺癌恶性细胞骨架机制提供了新的研究靶点。
更新日期：2021-06-22
中文翻译：
剪切应力引发圆形背侧褶边形成，促进癌细胞迁移
圆形背侧皱褶（CDRs）是一种富含F-肌动蛋白的特殊环状膜结构，与肿瘤的侵袭转移密切相关。剪切应力是影响肿瘤细胞命运的生物物理因素之一。然而，剪切应力如何促进 CDR 的形成仍不清楚。在这项研究中，我们发现剪切应力刺激CDR的形成并促进人乳腺MDA-MB-231癌细胞的迁移。整合素连接激酶 (ILK) 介导 ADP-核糖基化因子 (ARAP1/Arf1) 向 CDR 的募集。同时，转染ARAP1或Arf1突变体可以减少带有CDR的细胞数量、CDR面积和周长，从而阻断癌细胞的迁移。这表明ARAP1/Arf1对于CDR的形成和癌细胞迁移是必需的。进一步研究发现，剪切应力可以刺激细胞内巨胞饮作用（MPS）的形成，从而促进ARAP1/Arf1转运至早期内体，从而在CDR解聚后调节癌细胞迁移。我们的研究阐明了CDR的形成对于剪切应力诱导的乳腺癌细胞迁移至关重要，这为探索乳腺癌恶性细胞骨架机制提供了新的研究靶点。
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