scholarly journals Adipsin-Dependent Secretion of Hepatocyte Growth Factor Regulates the Adipocyte-Cancer Stem Cell Interaction

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4238
Author(s):  
Masahiro Mizuno ◽  
Behnoush Khaledian ◽  
Masao Maeda ◽  
Takanori Hayashi ◽  
Seiya Mizuno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Growth Factor ◽  
Cancer Stem Cell ◽  
Hepatocyte Growth Factor ◽  
Tumor Formation ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Hepatocyte Growth

Adipose tissue is a component of the tumor microenvironment and is involved in tumor progression. We have previously shown that adipokine adipsin (CFD) functions as an enhancer of tumor proliferation and cancer stem cell (CSC) properties in breast cancers. We established the Cfd-knockout (KO) mice and the mammary adipose tissue-derived stem cells (mADSCs) from them. Cfd-KO in mADSCs significantly reduced their ability to enhance tumorsphere formation of breast cancer patient-derived xenograft (PDX) cells, which was restored by the addition of Cfd in the culture medium. Hepatocyte growth factor (HGF) was expressed and secreted from mADSCs in a Cfd-dependent manner. HGF rescued the reduced ability of Cfd-KO mADSCs to promote tumorsphere formation in vitro and tumor formation in vivo by breast cancer PDX cells. These results suggest that HGF is a downstream effector of Cfd in mADSCs that enhances the CSC properties in breast cancers.

scholarly journals HGF/c-Met Promote Renal Carcinoma Cancer Stem Cells Enrichment Through Upregulation of Cir-CCDC66

2020 ◽  
Vol 19 ◽  
pp. 153303381990111 ◽  
Author(s):  
Juhong Yang ◽  
Lei Yang ◽  
Shen Li ◽  
Ning Hu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Hepatocyte Growth Factor ◽  
Renal Carcinoma ◽  
Cell Enrichment ◽  
Factor C ◽  
Hepatocyte Growth

Increasing studies have suggested that circular RNAs play an important function in the process of numerous cancers. We aimed to investigate the possible role of cir-CCDC66 in renal carcinoma cancer. As cancer stem cells are responsible for the renal carcinoma cancer tumor growth and resistance to conventional therapy, we focus on the cir-CCDC66 influence on renal carcinoma cancer stem cells. In this study, we performed experiments in human renal tubular epithelial cell HK2 cells and several renal carcinoma cancer cancer cell lines. The results showed that cir-CCDC66 was upregulated not only in renal carcinoma cancer cancer cell lines but also in cancer stem cell spheres. What’s more, the results showed that cir-CCDC66 enhanced the cancer stem cell enrichment. Further mechanistic studies showed that hepatocyte growth factor/c-Met pathway was activated in cancer stem cell enrichment and responsible for the cir-CCDC66 upregulation. Inhibition of hepatocyte growth factor/c-Met could block cir-CCDC66-induced cancer stem cell enrichment. In conclusion, our research revealed a novel mechanism between hepatocyte growth factor/c-Met/cir-CCDC66 and cancer stem cell enrichment. We verified that cir-CCDC66 could be a promising biomarker and therapy target for renal carcinoma cancer treatment.

scholarly journals Timosaponin AIII Suppresses Hepatocyte Growth Factor-Induced Invasive Activity through Sustained ERK Activation in Breast Cancer MDA-MB-231 Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chung-Hsin Tsai ◽  
Chu-Wen Yang ◽  
Jir-You Wang ◽  
Yi-Fang Tsai ◽  
Ling-Ming Tseng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Subsequent Increase ◽  
Concentration Dependent Manner ◽  
Erk Activation ◽  
Hepatocyte Growth ◽  
Timosaponin Aiii

Background. The aim of this study was to investigate the mechanisms by which Timosaponin AIII (TAIII) is able to inhibit HGF-induced invasion activity in the triple negative breast cancer cell line MDA-MB-231.Methods. After pretreatment with different concentrations (10−6~10−8 M) of TAIII, the cells were treated with hepatocyte growth factor (HGF, 15 ng/mL). At different time intervals after coincubation, various parameters, including the expression of c-Met, ERK, COX2, and MMP-9, which were assessed by Western blotting or by real-time PCR, were analyzed. In addition, invasive activity was also monitored.Results. HGF was found to induce c-MET activation and ERK activation, together with increased COX2 protein expression; these changes were followed by a subsequent increase in invasive activity. TAIII was found to suppress HGF-induced invasive activity andCOX2gene expression in a concentration-dependent manner (10−6~10−8 M) in parallel with increases in the phosphoforms of c-Met and ERK after TAIII treatment. The mechanisms by which TAIII suppresses HGF-induced invasive activity were demonstrated to include sustained cytoplasmic and nuclear ERK activation; these led to a suppression of nuclear ATF2 activation, which was followed by downregulation ofCOX2andMMP-9transcription.Conclusion. TAIII suppresses HGF-induced invasive activity in MDA-MB-231 cells via sustained ERK activation.

Epithelial cell spreading induced by hepatocyte growth factor influences paxillin protein synthesis and posttranslational modification

2004 ◽  
Vol 287 (4) ◽  
pp. G886-G898 ◽  
Author(s):  
Ann M. Hopkins ◽  
Matthias Bruewer ◽  
G. Thomas Brown ◽  
A’Drian A. Pineda ◽  
Julie J. Ha ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Hepatocyte Growth Factor ◽  
Fluorescent Protein ◽  
Kinase Inhibitor ◽  
Dominant Negative ◽  
Dependent Manner ◽  
Epithelial Migration ◽  
Cell Matrix ◽  
Hepatocyte Growth

Superficial wounds in the gastrointestinal tract rapidly reseal by coordinated epithelial cell migration facilitated by cytokines such as hepatocyte growth factor (HGF)/scatter factor released in the wound vicinity. However, the mechanisms by which HGF promotes physiological and pathophysiologic epithelial migration are incompletely understood. Using in vitro models of polarized T84 and Caco-2 intestinal epithelia, we report that HGF promoted epithelial spreading and RhoA GTPase activation in a time-dependent manner. Inducible expression of enhanced green fluorescent protein-tagged dominant-negative RhoA significantly attenuated HGF-induced spreading. HGF expanded a zone of partially flattened cells behind the wound edge containing basal F-actin fibers aligned in the direction of spreading. Concomitantly, plaques positive for the focal adhesion protein paxillin were enhanced. HGF induced an increase in the translation of paxillin and, to a lesser extent, β1-integrin. This was independent of cell-matrix adhesion through β1-integrin. Subcellular fractionation revealed increased cosedimentation of paxillin with plasma membrane-containing fractions following HGF stimulation, without corresponding enhancements in paxillin coassociation with β1 integrin or actin. Tyrosine phosphorylation of paxillin was reduced by HGF and was sensitive to the Src kinase inhibitor PP2. With these taken together, we propose that HGF upregulates a free cytosolic pool of paxillin that is unaffiliated with either the cytoskeleton or focal cell-matrix contacts. Thus early spreading responses to HGF may partly relate to increased paxillin availability for incorporation into, and turnover within, dynamic cytoskeletal/membrane complexes whose rapid and transient adhesion to the matrix drives migration.

scholarly journals NQO1 is Required for β-Lapachone-Mediated Downregulation of Breast-Cancer Stem-Cell Activity

2018 ◽  
Vol 19 (12) ◽  
pp. 3813 ◽  
Author(s):  
Dong Kim ◽  
Je-Yoel Cho
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Stem Cell ◽  
Breast Cancer Stem Cell ◽  
Cancer Development ◽  
Dependent Manner ◽  
Mammosphere Formation

Cancer stem cells (CSCs) exhibit self-renewal activity and give rise to other cell types in tumors. Due to the infinite proliferative potential of CSCs, drugs targeting these cells are necessary to completely inhibit cancer development. The β-lapachone (bL) compound is widely used to treat cancer development; however, its effect on cancer stem cells remain elusive. Thus, we investigated the effect of bL on mammosphere formation using breast-cancer stem-cell (BCSC) marker-positive cells, MDA-MB-231. MDA-MB-231 cells, which are negative for reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H):quinone oxidoreductase (NQO1) expression, were constructed to stably express NQO1 (NQO1 stable cells). The effect of bL on these cells was evaluated by wound healing and Transwell cell-culture chambers, ALDEFLUOR assay, and mammosphere formation assay. Here, we show that bL inhibited the proliferative ability of mammospheres derived from BCSC marker-positive cells, MDA-MB-231, in an NQO1-dependent manner. The bL treatment efficiently downregulated the expression level of BCSC markers cluster of differentiation 44 (CD44), aldehyde dehydrogenase 1 family member A1 (ALDH1A1), and discs large (DLG)-associated protein 5 (DLGAP5) that was recently identified as a stem-cell proliferation marker in both cultured cells and mammosphered cells. Moreover, bL efficiently downregulated cell proliferation and migration activities. These results strongly suggest that bL could be a therapeutic agent for targeting breast-cancer stem-cells with proper NQO1 expression.

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