Yonggang Lv1,2, Xiaomei Zhang3,4, Lini Chen3,4. 1. Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, 174 Shazheng Street, Shapingba District, Chongqing, 400044, People's Republic of China. yglv@cqu.edu.cn. 2. Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China. yglv@cqu.edu.cn. 3. Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, 174 Shazheng Street, Shapingba District, Chongqing, 400044, People's Republic of China. 4. Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.
Abstract
OBJECTIVES: The mechanical forces on circulating tumor cells (CTCs) should not be ignored in blood and it is more essential that CTCs can overcome and utilize the mechanical interaction to acquire the ability of distant metastasis. At present there are few studies on how suspension mechanics regulates the behavior of tumor cells. The aim of the study was to explore the effects of suspension state on the epithelial-mesenchymal transition (EMT) and stemness of breast CTCs and the molecular mechanisms involved. RESULTS: Suspension state could regulate the program of EMT in breast cancer cells, which supported the complex dynamic concept of EMT. It is that the Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) signaling pathway was activated by suspension state in MCF-7 cells instead of MDA-MB-231 cells. In addition, suspension state increased the stemness of breast cancer cells from different aspects. CONCLUSION: The study highlighted the emergence of hybrid epithelial/mesenchymal (E/M) state during hematogenous metastasis and the plasticity of CTCs caused by cancer stem cells, further providing novel insights into clinical monitoring of CTCs and therapeutic strategies.
OBJECTIVES: The mechanical forces on circulating tumor cells (CTCs) should not be ignored in blood and it is more essential that CTCs can overcome and utilize the mechanical interaction to acquire the ability of distant metastasis. At present there are few studies on how suspension mechanics regulates the behavior of tumor cells. The aim of the study was to explore the effects of suspension state on the epithelial-mesenchymal transition (EMT) and stemness of breast CTCs and the molecular mechanisms involved. RESULTS: Suspension state could regulate the program of EMT in breast cancer cells, which supported the complex dynamic concept of EMT. It is that the Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) signaling pathway was activated by suspension state in MCF-7 cells instead of MDA-MB-231 cells. In addition, suspension state increased the stemness of breast cancer cells from different aspects. CONCLUSION: The study highlighted the emergence of hybrid epithelial/mesenchymal (E/M) state during hematogenous metastasis and the plasticity of CTCs caused by cancer stem cells, further providing novel insights into clinical monitoring of CTCs and therapeutic strategies.
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