Growth-induced stress enhances epithelial-mesenchymal transition induced by IL-6 in clear cell renal cell carcinoma via the Akt/GSK-3β/β-catenin signaling pathway

Chen, Qiwei; Yang, Deyong; Zong, Hong; Zhu, Lei; Wang, L; Wang, X; Zhu, Xinqing; Song, Xishuang; Wang, J

doi:10.1038/oncsis.2017.74

Cited by 64 publications

(64 citation statements)

References 44 publications

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“…The level of expression of β‐catenin also directly impacts the activation of the Wnt signal pathway . When the degradation of β‐catenin becomes an obstacle, too much β‐catenin accumulates in the endonuclear membrane leading to cancer via an abnormal activation of the Wnt signal pathway . In 2012, Tanya et al reported that the function of Trop2 requires the presence of β‐catenin in nucleus.…”

Section: Discussionmentioning

confidence: 99%

The role and molecular mechanism of Trop2 induced epithelial‐mesenchymal transition through mediated β‐catenin in gastric cancer

et al. 2019

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The present study elucidates the potential role of Trop2 in tumor invasion and the promotion of epithelial‐mesenchymal transition (EMT) when binding β‐catenin in GC. The role of Trop2 in promoting EMT in GC cells was examined by a variety of experimental assays. Moreover, the underlying molecular mechanism of Trop2 in promoting EMT was studied by in vivo and in vitro assays. The Trop2 expression in relation to tumor metastasis status was detected by IHC in 248 cases of GC tissues and 86 cases of matched adjacent tissues. Trop2 promoted the metastasis and induces EMT in GC. Meanwhile, the elevated protein levels of Trop2 and mesenchymal markers were also found in the TGF‐β1‐induced EMT model in GC cells. Importantly, Trop2 physically bound and activated β‐catenin to promote EMT; moreover, Trop2 increased the accumulation of β‐catenin in the nucleus to accelerate metastasis in GC cells. Inhibition of Trop2 expression in GC cells prevented the migration and invasion of GC cells in vivo. Trop2+/vimentin+ expression was higher in GC tissues than that in matched adjacent tissues, and Trop2+/vimentin+ expression in GC was associated with the differentiation, TNM stage, and distant metastases. These sets of data reveal a novel regulatory network of Trop2 in EMT and GC metastasis, suggesting Trop2 as a useful marker for inducing EMT and metastasis of GC, which may help to lead a better understanding of the pathogenesis of the GC.

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Section: Discussionmentioning

confidence: 99%

The role and molecular mechanism of Trop2 induced epithelial‐mesenchymal transition through mediated β‐catenin in gastric cancer

et al. 2019

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“…Several other alternative set-ups have been developed to apply a defined stress on an entire cell population for prolonged periods of time, by embedding them in agarose [12] or in extracellular matrix [47] or using a transmembrane-based pressure device [48]. The drawback of such devices is that they are not compatible with high-resolution microscopy due to the thickness of the gels or the transwell geometry.…”

Section: Discussionmentioning

confidence: 99%

Development of a soft cell confiner to decipher the impact of mechanical stimuli on cells

Prunet

Lefort

Delanoë-Ayari

et al. 2020

Preprint

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Emerging evidence suggests the importance of mechanical stimuli in normal and pathological situations for the control of many critical cellular functions. While the effect of matrix stiffness has been and is still extensively studied, few studies have focused on the role of mechanical stresses. The main limitation of such analyses is the lack of standard in vitro assays enabling extended mechanical stimulation compatible with dynamic biological and biophysical cell characterization. We have developed an agarose-based microsystem, the soft cell confiner, which enables the precise control of confinement for single or mixed cell populations. The rigidity of the confiner matches physiological conditions and enables passive medium renewal. It is compatible with time-lapse microscopy, in situ immunostaining, and standard molecular analyses, and can be used with both adherent and nonadherent cell lines. Cell proliferation of various cell lines (hematopoietic cells, MCF10A epithelial breast cells and HS27A stromal cells) was followed for several days up to confluence using video-microscopy and further documented by Western blot and immunostaining. Interestingly, even though the nuclear projected area was much larger upon confinement, with many highly deformed nuclei (non-circular shape), cell viability, assessed by live and dead cell staining, was unaffected for up to 8 days in the confiner. However, there was a decrease in cell proliferation upon confinement for all tested cell lines. The soft cell confiner is thus a valuable tool to decipher the effect of long-term confinement and deformation on the biology of cell populations. This tool will be instrumental in deciphering the impact of nuclear and cytoskeletal mechanosensitivity in normal and pathological conditions involving highly confined situations, such as those reported upon aging with fibrosis or during cancer. Highlights-We have developed a flexible hydrogel-based microsystem that precisely confines cells for extended periods of time with controlled nutrient levels.-The soft confiner system was validated for both adherent and non-adherent cells and allows the simultaneous in situ follow-up or ex situ analysis of multiple subpopulations.-A unique tool to analyze the role of long-term effect of mechanical confinement in normal and pathological conditions. Graphical abstract3/27

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“…The TGF-β-induced upregulation of α-SMA and CD44 in LX-2 cells was blocked by βelemene [117]. In addition to CD44, α-SMA is produced when fibroblasts are stimulated and is essential for cell movement, tumor development, and invasion [118,119].…”

Section: β-Elemene Alters Inflammation and Thementioning

confidence: 99%

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

Xie

Lei

et al. 2020

BioMed Research International

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Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.

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Growth-induced stress enhances epithelial-mesenchymal transition induced by IL-6 in clear cell renal cell carcinoma via the Akt/GSK-3β/β-catenin signaling pathway

Cited by 64 publications

References 44 publications

The role and molecular mechanism of Trop2 induced epithelial‐mesenchymal transition through mediated β‐catenin in gastric cancer

The role and molecular mechanism of Trop2 induced epithelial‐mesenchymal transition through mediated β‐catenin in gastric cancer

Development of a soft cell confiner to decipher the impact of mechanical stimuli on cells

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

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