Salinomycin attenuates liver cancer stem cell motility by enhancing cell stiffness and increasing F-actin formation via the FAK-ERK1/2 signalling pathway

Sun, Jinghui; Luo, Qing; Liu, Lingling; Xianjiong, Yang; Zhu, Shunqin; Song, Guanbin

doi:10.1016/j.tox.2017.04.006

Cited by 45 publications

(35 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, FAK and the extracellular signal-regulated kinase (ERK1/2) pathway are involved in the regulation of growth and metastasis of liver cancer stem cells (LCSCs) [23]. The use of the anticancer drug salinomycin inhibited the activity of FAK and ERK1/2, resulting in the increased stiffness of LCSCs [24]. Another study has shown that changes in the stiffness of living cells might affect numerous cellular physiological activities [25].…”

Section: Introductionmentioning

confidence: 99%

The roles of nuclear focal adhesion kinase (FAK) on Cancer: a focused review

Zhou

Qian

Tang

2019

J Exp Clin Cancer Res

217

158

View full text Add to dashboard Cite

FAK is a tyrosine kinase overexpressed in cancer cells and plays an important role in the progression of tumors to a malignant phenotype. Except for its typical role as a cytoplasmic kinase downstream of integrin and growth factor receptor signaling, related studies have shown new aspects of the roles of FAK in the nucleus. FAK can promote p53 degradation through ubiquitination, leading to cancer cell growth and proliferation. FAK can also regulate GATA4 and IL-33 expression, resulting in reduced inflammatory responses and immune escape. These findings establish a new model of FAK from the cytoplasm to the nucleus. Activated FAK binds to transcription factors and regulates gene expression. Inactive FAK synergizes with different E3 ligases to promote the turnover of transcription factors by enhancing ubiquitination. In the tumor microenvironment, nuclear FAK can regulate the formation of new blood vessels, affecting the tumor blood supply. This article reviews the roles of nuclear FAK in regulating gene expression. In addition, the use of FAK inhibitors to target nuclear FAK functions will also be emphasized.

show abstract

Section: Introductionmentioning

confidence: 99%

The roles of nuclear focal adhesion kinase (FAK) on Cancer: a focused review

Zhou

Qian

Tang

2019

J Exp Clin Cancer Res

217

158

View full text Add to dashboard Cite

show abstract

“…The cancer preventive activity of EGCG was effectively found in stiffened cells and in the tumour sphere formation of H1299-sdCSCs. Sun et al reported that salinomycin, one of the most potent anti-CSC compounds screened by Weinburg et al, increases liver CSC stiffness in a manner similar to that of EGCG 28,29 .…”

Section: Discussionmentioning

confidence: 99%

(−)-Epigallocatechin gallate inhibits stemness and tumourigenicity stimulated by AXL receptor tyrosine kinase in human lung cancer cells

Namiki

Wongsirisin

Yokoyama

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Cancer stem cells (H1299-sdCSCs) were obtained from tumour spheres of H1299 human lung cancer cells. We studied low stiffness, a unique biophysical property of cancer cells, in H1299-sdCSCs and parental H1299. Atomic force microscopy revealed an average Young's modulus value of 1.52 kPa for H1299-sdCSCs, which showed low stiffness compared with that of H1299 cells, with a Young's modulus value of 2.24 kPa. (−)-Epigallocatechin gallate (EGCG) reversed the average Young's modulus value of H1299-sdCSCs to that of H1299 cells. EGCG treatment inhibited tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. AXL receptor tyrosine kinase is highly expressed in H1299-sdcScs and AXL knockdown with siAXLs significantly reduced tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. An AXL-high population of H1299-sdCSCs was similarly reduced by treatment with EGCG and siAXLs. Transplantation of an AXL-high clone isolated from H1299 cells into SCID/Beige mice induced faster development of bigger tumour than bulk H1299 cells, whereas transplantation of the AXL-low clone yielded no tumours. Oral administration of EGCG and green tea extract (GTE) inhibited tumour growth in mice and reduced p-AXL, ALDH1A1, and SLUG in tumours. Thus, EGCG inhibits the stemness and tumourigenicity of human lung cancer cells by inhibiting AXL. Green tea and (−)-epigallocatechin gallate (EGCG), the main constituent of green tea catechins, prevent cancer in humans, as demonstrated in phase II clinical trials, which showed that EGCG prevented colorectal adenoma recurrence and prostate cancer development from high-grade prostate intraepithelial neoplasia 1-4. Numerous investigators have reported therapeutic effects in various human cancer cell lines by combining EGCG and other green tea catechins with anticancer compounds, including anticancer drugs, nonsteroidal anti-inflammatory drugs, and phytochemicals 5,6. Because EGCG inhibits the expression of stemness marker genes and epithelialmesenchymal transition (EMT)-related genes in human cancer stem cells (CSCs) of the breast, lung, prostate and liver, CSCs are targets of EGCG for cancer prevention and therapy 7. Using atomic force microscopy (AFM), Gimzewski's laboratory first reported that metastatic cancer cells obtained from the pleural fluids of various cancer patients showed lower average Young's modulus values, indicating lower cell stiffness, than those of normal mesothelial cells from pleural effusion 8. Furthermore, they showed that treatment with green tea extract (GTE) increased the average Young's modulus values for metastatic cancer cells (i.e., reversed the values to those of normal cell stiffness levels) 9. Our previous study revealed that EGCG increased the stiffness of H1299 and Lu99 human non-small cell lung cancer (NSCLC) cells, inhibited the high expression of EMT-related proteins, such as vimentin and SLUG, and reduced cell motility 10. To investigate the inhibitory effects of EGCG on the biophysical properties of CSCs, we enriched CSCs from the tumour spheres of

show abstract

“…CSCs are believed to play an important role in metastasis, the deadliest cancer progression. Multiple researchers have shown salinomycin decreases CSC invasiveness and migration (44)(45)(46)(47). This physiologic change is associated with the FAK-ERK1/2 signaling pathway in liver CSCs (44) and the abolition of STAT3 and STAT1 interactions in colorectal CSCs (45).…”

Section: Salinomycin's Effect On Csc Stemnessmentioning

confidence: 99%

“…Multiple researchers have shown salinomycin decreases CSC invasiveness and migration (44)(45)(46)(47). This physiologic change is associated with the FAK-ERK1/2 signaling pathway in liver CSCs (44) and the abolition of STAT3 and STAT1 interactions in colorectal CSCs (45). Salinomycin has also been shown to differentiate CSCs, transforming them from their chemoresistant and tumorogenic state to a state that can be eliminated by common chemotherapeutics (46,48).…”

Section: Salinomycin's Effect On Csc Stemnessmentioning

confidence: 99%

Salinomycin's potential to eliminate glioblastoma stem cells and treat glioblastoma multiforme (Review)

Magrath

Kim

2017

International Journal of Oncology

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is the most common and deadliest form of primary brain tumor. Despite treatment with surgery, radiotherapy, and chemotherapy with the drug temozolomide, the expected survival after diagnosis remains low. The median survival is only 14.6 months and the two-year survival is a mere 30%. One reason for this is the heterogeneity of GBM including the presence of glioblastoma cancer stem cells (GSCs). GSCs are a subset of cells with the unique ability to proliferate, differentiate, and create tumors. GSCs are resistant to chemotherapy and radiation and thought to play an important role in recurrence. In order to effectively treat GBM, a drug must be identified that can kill GSCs. The ionophore salinomycin has been shown to kill cancer stem cells and is therefore a promising future treatment for GBM. This study focuses on salinomycin's potential to treat GBM including its ability to reduce the CSC population, its toxicity to normal brain cells, its mechanism of action, and its potential for combination treatment.

show abstract

Salinomycin attenuates liver cancer stem cell motility by enhancing cell stiffness and increasing F-actin formation via the FAK-ERK1/2 signalling pathway

Cited by 45 publications

References 56 publications

The roles of nuclear focal adhesion kinase (FAK) on Cancer: a focused review

The roles of nuclear focal adhesion kinase (FAK) on Cancer: a focused review

(−)-Epigallocatechin gallate inhibits stemness and tumourigenicity stimulated by AXL receptor tyrosine kinase in human lung cancer cells

Salinomycin's potential to eliminate glioblastoma stem cells and treat glioblastoma multiforme (Review)

Contact Info

Product

Resources

About