Activation of AKT signaling promotes epithelial–mesenchymal transition and tumor growth in colorectal cancer cells

Suman, Suman; Kurisetty, Vittal; Das, Trinath P.; Vadodkar, Aditi; Ramos, Gabriel; Lakshmanaswamy, Rajkumar; Damodaran, Chendil

doi:10.1002/mc.22076

Cited by 76 publications

(70 citation statements)

References 49 publications

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“…In accordance to our study, it was reported that ERKTwist and PI3K/AKT-Twist pathway existed in many cancers and directly or indirectly promoted cell survival, motility, and invasion in EMT development [21][22][23]. Based on the cell Fig.…”

Section: Discussionsupporting

confidence: 89%

RETRACTED ARTICLE: CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma

Yao

Song

et al. 2015

Mol Neurobiol

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In recent decades, the chemokine receptor CXCR4 and its ligand CXCL12 have been extensively reported to be associated with tumorigenesis. In addition, Twist signaling induces the epithelial-mesenchymal transition (EMT) process in glioblastoma development. In the present study, in vitro assays were used to investigate the role of CXCR4 and Twist in human glioblastoma. We explored the impact of CXCR4 and Twist on human glioblastoma using in vitro protein and gene assays. We found the administration of CXCL12 upregulated the expression of p-ERK, p-AKT, Twist, N-cadherin, and MMP9 in U87 cells, whereas the increase of E-cadherin protein was affected. Subsequently, Twist activity and EMT signaling were directly influenced by PD98059 and LY294002. Most importantly, the genetic silencing of Twist inhibited CXCL12-induced EMT occurrence, including proliferation, migration, and tumor formation of U87 cells. In conclusion, CXCL12/CXCR4 pathway activates ERK and PI3K/AKT signaling to upregulate Twist pathway, leading to the progression of EMT in human glioblastoma. Our study creates a new stage for molecule-targeted therapy of human glioblastoma.

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Section: Discussionsupporting

confidence: 89%

RETRACTED ARTICLE: CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma

Yao

Song

et al. 2015

Mol Neurobiol

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“…It is known that the MAP kinase and Akt pathways play important roles in colon cancer cell invasion and migration (Tremblay et al 2006, Huynh et al 2010, Slattery et al 2012. The activation of Akt signaling promotes EMT and tumor growth in colon cancer cells (Suman et al 2014). In the present study, we showed that BDNF induced cell motility and upregulated VEGF expression via the induction of HO-1.…”

Section: Discussionsupporting

confidence: 56%

Brain-derived neurotrophic factor regulates cell motility in human colon cancer

Huang¹,

Lin²,

Lin³

et al. 2015

Endocrine-Related Cancer

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Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to affect cancer cell metastasis and migration. In the present study, we investigated the mechanisms of BDNF-induced cell migration in colon cancer cells. The migratory activities of two colon cancer cell lines, HCT116 and SW480, were found to be increased in the presence of human BDNF. Heme oxygenase-1 (HO)-1 is known to be involved in the development and progression of tumors. However, the molecular mechanisms that underlie HO-1 in the regulation of colon cancer cell migration remain unclear. Expression of HO-1 protein and mRNA increased in response to BDNF stimulation. The BDNF-induced increase in cell migration was antagonized by a HO-1 inhibitor and HO-1 siRNA. Furthermore, the expression of vascular endothelial growth factor (VEGF) also increased in response to BDNF stimulation, as did VEGF mRNA expression and transcriptional activity. The increase in BDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Moreover, transfection with HO-1 siRNA effectively reduced the increased VEGF expression induced by BDNF. The BDNF-induced cell migration was regulated by the ERK, p38, and Akt signaling pathways. Furthermore, BDNF-increased HO-1 and VEGF promoter transcriptional activity were inhibited by ERK, p38, and AKT pharmacological inhibitors and dominantnegative mutants in colon cancer cells. These results indicate that BDNF increases the migration of colon cancer cells by regulating VEGF/HO-1 activation through the ERK, p38, and PI3K/Akt signaling pathways. The results of this study may provide a relevant contribution to our understanding of the molecular mechanisms by which BDNF promotes colon cancer cell motility.

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“…However, most CRC cases with PI3K mutations also carry mutations in KRAS 51 . The activated PI3K further activates AKT1 and AKT2, which then enhances tumor growth by promoting epithelial to mesenchymal transition (EMT) 52,53 . Loss-of-function mutations in PTEN, which is a tumor suppressor and an antagonist of the PI3K/AKT pathway, induce AKT-regulated metastasis in CRCs 54 .…”

Section: Mutational Landscape In Chromosomal Instabilitymentioning

confidence: 99%

Colorectal cancer carcinogenesis: a review of mechanisms

Tariq¹,

Ghias²

2016

Cancer Biology &Amp; Medicine

233

138

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Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men globally. CRC arises from one or a combination of chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. Non-coding RNAs, more importantly microRNAs and long non-coding RNAs have also been implicated at various CRC stages. Understanding the specific mechanisms of tumorigenesis and the underlying genetic and epigenetic traits is critical in comprehending the disease phenotype. This paper reviews these mechanisms along with the roles of various non-coding RNAs in CRCs.

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Activation of AKT signaling promotes epithelial–mesenchymal transition and tumor growth in colorectal cancer cells

Cited by 76 publications

References 49 publications

RETRACTED ARTICLE: CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma

RETRACTED ARTICLE: CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma

Brain-derived neurotrophic factor regulates cell motility in human colon cancer

Colorectal cancer carcinogenesis: a review of mechanisms

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