title: Salinomycin attenuates liver cancer stem cell motility by enhancing cell stiffness and increasing F-actin formation via the FAK-ERK1/2 signalling pathway.
abstract: Salinomycin has recently been identified as an antitumour drug for several types of cancer stem cell (CSC) treatments. However, the effects of salinomycin on the migratory and invasive properties of liver cancer stem cells (LCSCs) are unclear. In present study, we investigated the effect of salinomycin on the migration and invasion of LCSCs, and examined the molecular mechanisms underlying the anticancer effects of salinomycin. Here we showed that the migration and invasion of LCSCs were significantly suppressed in a salinomycin dose-dependent manner. Moreover, western blot analysis showed that salinomycin repressed the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK1/2). Taken together, these findings provide new evidence that salinomycin suppresses the migration and invasion of LCSCs by inhibiting the expression of the FAK-ERK1/2 signalling pathway. In addition, the analysis of the mechanical properties showed that salinomycin increased cell stiffness in LCSCs via the FAK, and ERK1/2 pathways, suggesting that the inhibition of LCSC migration might partially contribute to the increase in cell stiffness stimulated by salinomycin. To further examine the role of salinomycin on cell motility and stiffness, the actin cytoskeleton of LCSCs was detected. The increased F-actin filaments in LCSCs induced by salinomycin reflected the increase in cell stiffness and the decrease in cell migration. Overall, these results showed that salinomycin inhibits the migration and invasion of LCSCs through the dephosphorylated FAK and ERK1/2 pathways, reflecting the changes in cell stiffness resulting from the increased actin cytoskeleton.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China; School of Medical Laboratory Science, Chengdu Medical College, Chengdu 610500, People's Republic of China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China; Department of Chemistry, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 500025, People's Republic of China.
authors.forename: Xianjiong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China; School of Life Sciences, Southwest University, Chongqing 400715, People's Republic of China.
authors.forename: Shunqin
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, People's Republic of China. Electronic address: song@cqu.edu.cn.
authors.forename: Guanbin
authors.initials: G
authors.lastname: Song
mesh_terms: D000199:Actins / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003049:Coccidiostats / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011714:Pyrans / Q000494:pharmacology*; D000095662:Polyether Polyketides
chemical_list: D000199:Actins; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D003049:Coccidiostats; D048049:Extracellular Signal-Regulated MAP Kinases; D051417:Focal Adhesion Kinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides; C496050:PTK2 protein, human; C522361:MMP2 protein, human; C579270:MMP9 protein, human
keywords: Actin cytoskeleton; Cell motility; Cell stiffness; FAK-ERK1/2 signalling pathway; Liver cancer stem cells; Salinomycin