Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters

Li, Junlin; Zhou, Binhua P.

doi:10.1186/1471-2407-11-49

Cited by 300 publications

(252 citation statements)

References 35 publications

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“…It was generally believed that ROS exert cytotoxic and genotoxic effects by causing damage to lipids, proteins and DNA, because of their greater chemical reactivity with regard to oxygen [15,21]. Recently, however, ROS was proposed to be involved in tumor metastasis as a second-messenger for regulation of diverse cellular processes.…”

Section: Discussionmentioning

confidence: 99%

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Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways

Yang

Li²,

Xu³

et al. 2013

neo

100

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Colorectal cancer (CRC), one of the most common human malignancies, is a major public health problem in the developed world. Capsaicin, widely used as a food additive and as an analgesic agent, is a major pungent ingredient of red pepper. Though capsaicin-induced apoptosis was previously reported in cancer cells, relatively little is known about the impact of capsaicin on other aspect of cancer cell behavior. In this study, we demonstrated that treatment with high-concentration of capsaicin (≥ 200 µM for SW480 and CT-26 cell lines; ≥ 25 µM for HCT116 cell line) inhibited CRC cell proliferation in a dose-dependent manner. In spite of no anti-proliferative effect, notably, low-concentration of capsaicin (100 µM for SW480 and CT-26 cell lines; 12.5 µM for HCT116 cell line) enhanced both migratory and invasive capability of these cells, which was validated by both in vitro and in vivo model. Further, we showed that 100 µM capsaicin induced epithelial-to-mesenchymal (EMT), up-regulated expression of MMP-2 and MMP-9, and activated Akt/mTOR and STAT-3 pathways in SW480 cells. Finally, we showed that capsaicin-induced metastasis of CRC cells was mediated by modulating reactive oxygen species (ROS) production. Our findings are considered as a significant step toward a better understanding of capsaicin-associated regulatory network on CRC cells.

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Section: Discussionmentioning

confidence: 99%

“…It is reported that both Akt/mTOR and STAT-3 pathways were upstream pathways controlling both EMT and expression of MMP-2 and MMP-9 [15][16][17][18]. Therefore, we wanted to determine whether PI3K/Akt and STAT-3 pathways were activated upon low-concentration capsaicin treatment.…”

Section: Low-concentration Capsaicin Promotes Migration and Invasionmentioning

confidence: 99%

Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways

Yang

Li²,

Xu³

et al. 2013

neo

100

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“…Twist1 expression downregulates E-cadherin, but upregulates the EMT markers CD44, Slug (also known as SNAI2) and Snail Li and Zhou, 2011;Casas et al, 2011). Thus, we initially tested their promoter activities using the corresponding luciferase plasmids.…”

Section: Aurka and Twist1 In Emtmentioning

confidence: 99%

The Aurora-A–Twist1 axis promotes highly aggressive phenotypes in pancreatic carcinoma

Wang

Nikhil

Viccaro

et al. 2017

Journal of Cell Science

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We uncovered a crucial role for the Aurora kinase A (AURKA)-Twist1 axis in promoting epithelial-to-mesenchymal transition (EMT) and chemoresistance in pancreatic cancer. Twist1 is the first EMT-specific target of AURKA that was identified using an innovative screen. AURKA phosphorylates Twist1 at three sites, which results in its multifaceted regulation -AURKA inhibits its ubiquitylation, increases its transcriptional activity and favors its homodimerization. Twist1 reciprocates and prevents AURKA degradation, thereby triggering a feedback loop. Ablation of either AURKA or Twist1 completely inhibits EMT, highlighting both proteins as central players in EMT progression. Phosphorylation-dead Twist1 serves as a dominant-negative and fully reverses the EMT phenotype induced by Twist1, underscoring the crucial role of AURKA-mediated phosphorylation in mediating Twist1-induced malignancy. Likewise, Twist1-overexpressing BxPC3 cells formed large tumors in vivo, whereas expression of phosphorylation-dead Twist1 fully abrogated this effect. Furthermore, immunohistochemical analysis of pancreatic cancer specimens revealed a 3-fold higher level of Twist1 compared to that seen in healthy normal tissues. This is the first study that links Twist1 in a feedback loop with its activating kinase, which indicates that concurrent inhibition of AURKA and Twist1 will be synergistic in inhibiting pancreatic tumorigenesis and metastasis.

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“…23 It has been reported that HIF-1 promotes EMT through direct regulation of EMT-related proteins, such as TWIST. 24 During EMT process, epithelial cell layers lose polarity together with cell-to-cell contacts. The expression of proteins that promote cell-to-cell contact, such as E-cadherin, may be lost, and the cells may acquire mesenchymal markers such as vimentin and the MMPs MMP-9, resulting in an enhanced ability for cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

Curcumin inhibits hypoxia-induced migration in K1 papillary thyroid cancer cells

Tan¹,

Zhang²,

Cheng³

et al. 2014

Exp Biol Med (Maywood)

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Curcumin, traditionally used as food and medicinal purposes, has recently been reported to have protective efficacy against hypoxia. Hypoxia is one of the important reactive factors in tumor metastasis, which is a key problem in clinical thyroid cancer therapy. In present study, we investigate the anti-metastatic effect of curcumin on the K1 papillary thyroid cancer cells as well as its potential mechanisms. The results show that curcumin effectively inhibits hypoxia-induced reactive oxygen species (ROS) upregulation and significantly decreases the mRNA and protein expression levels of hypoxia-inducible factor-1a (HIF-1a) in K1 cells. Curcumin also decreases the DNA binding ability of HIF-1a to hypoxia response element (HRE). Furthermore, curcumin enhances E-cadherin expression, inhibits metalloproteinase-9 (MMP-9) enzyme activity, and weakens K1 cells migration under hypoxic conditions. In summary, these results indicate that curcumin possesses a potent anti-metastatic effect and might be an effective tumoristatic agent for the treatment of aggressive papillary thyroid cancers.Keywords: Curcumin, K1 papillary thyroid cancer cell, hypoxia-inducible factor-1a, metastasis Experimental Biology and Medicine 2015; 240: 925-935.

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Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters

Cited by 300 publications

References 35 publications

Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways

Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways

The Aurora-A–Twist1 axis promotes highly aggressive phenotypes in pancreatic carcinoma

Curcumin inhibits hypoxia-induced migration in K1 papillary thyroid cancer cells

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