Integrin-linked kinase overexpression promotes epithelial-mesenchymal transition<i>via</i>nuclear factor-κB signaling in colorectal cancer cells

Shen, Hong; Ma, Junli; Zhang, Yan; Deng, Geng; Qu, Yanling; Wu, Xiaoling; He, Jingxuan; Zhang, Sai; Zeng, Shan

doi:10.3748/wjg.v22.i15.3969

Cited by 27 publications

(23 citation statements)

References 30 publications

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“…The current study verified that emodin weakened the migration and invasion abilities of A2780 and SK-OV-3 by inhibiting EMT via targeting ILK. This result is consistent with a previous study which confirmed that ILK overexpression promotes epithelial-mesenchymal transition in colorectal cancer cells [35]. …”

Section: Discussionsupporting

confidence: 94%

Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway

Xuan

et al. 2016

BioMed Research International

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Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite the anticancer capabilities of emodin observed in many cancers, including EOC, the underlying molecular mechanism remains to be elucidated. A crucial link has been discovered between the acquisition of metastatic traits and the epithelial-mesenchymal transition (EMT). The present study aimed to determine whether emodin could inhibit the EMT of EOC cells and explore the underlying mechanism. The CCK-8 assay and transwell assay showed that emodin effectively repressed the abilities of proliferation, invasion, and migration in A2780 and SK-OV-3 cells. The Western blot showed that emodin upregulated epithelial markers (E-cadherin and Claudin) while it downregulated mesenchymal markers (N-cadherin and Vimentin) and transcription factor (Slug) in a dose-dependent fashion. After transfection of siRNA-Slug, both Slug and N-cadherin were downregulated in EOC cells while E-cadherin was upregulated, which was intensified by emodin. Besides, emodin decreased the expression of ILK, p-GSK-3β, β-catenin, and Slug. Transfection of siRNA-ILK also achieved the same effects, which was further strengthened by following emodin treatment. Nevertheless, SB216763, an inhibitor of GSK-3β, could reverse the effects of emodin except for ILK expression. These findings suggest that emodin inhibited the EMT of EOC cells via ILK/GSK-3β/Slug signaling pathway.

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Section: Discussionsupporting

confidence: 94%

Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway

Xuan

et al. 2016

BioMed Research International

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“… 20 , 29 ILK has been reported to facilitate cancer cell migration and invasion by regulating EMT processes. 15 , 30 , 31 Consistently, the knockdown of ILK inhibited tumor invasion and metastasis by inhibiting the EMT process in bladder cancer and in oral squamous cell carcinoma. 17 , 32 In the present study, we found that the overexpression of ILK of A2780 and SK-OV-3 cells had a greater potential for proliferation, migration and invasion.…”

Section: Discussionmentioning

confidence: 68%

Emodin suppresses proliferation, migration and invasion in ovarian cancer cells by down regulating ILK in vitro and in vivo

Lu¹,

Xu²,

Zhao³

et al. 2017

OTT

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ObjectiveAlthough our previous studies have confirmed that 1, 3, 8-trihydroxy-6-methylant hraquinone (emodin) inhibits migration and invasion in epithelial ovarian cancer (EOC) cells, the underlying molecular mechanism remains unknown. Here, the aim was to investigate the effects of emodin on EOC cells and to study further the mechanism underlying this process, both in vitro and in vivo.Materials and methodsCell proliferation was evaluated by the methylthiazolyl tetrazolium assay. Cell migration and invasion abilities were tested using the transwell assay. The expression of integrin-linked kinase (ILK) and epithelial–mesenchymal transition (EMT)-associated factors were measured with western blotting.ResultsExogenous ILK enhanced the proliferation, migration and invasion properties of A2780 and SK-OV-3 cells. After treatment with emodin, the survival rate of cells was gradually reduced, including those of SK-OV-3/pLVX-ILK and A2780/pLVX-ILK cells, with increasing emodin concentrations. The migration and invasion abilities of A2780 and SK-OV-3 cells were effectively increased by the transfection of pLVX-ILK, which could be abrogated by following this with 48 hours of emodin treatment. Treatment with emodin significantly downregulated the expression of ILK and EMT-related proteins. So, emodin suppressed proliferation, migration and invasion in ovarian cancer cells by downregulating ILK in vitro. SK-OV-3/pLVX-Con and SK-OV-3/pLVX-ILK cells were used to generate xenografts in nude mice. Tumors grew more rapidly in the SK-OV-3/pLVX-ILK group compared with the control group, and this could be significantly inhibited by emodin. Also, the expression of E-cadherin was downregulated, while the expression of Slug, MMP-9 and Vimentin were upregulated in the SK-OV-3/pLVX-ILK group, and this could be reversed by following treatment with emodin. Emodin did not demonstrate target toxicity on hepatocytes, nephrocytes and cardiomyocytes.ConclusionEmodin suppresses proliferation, migration and invasion in ovarian cancer by targeting ILK.

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“…Among them, ILK was selected as key candidate based on the central signal transducing location in protein-protein interaction network and its key role in cancer progression and cancer cell motility. It has been proven that overexpression of ILK was crucial for carcinogenesis and metastasis in assorted cancer types, including colorectal cancer [8], renal cell carcinoma [11], thyroid cancer [12], breast cancer [6,13], non-small cell lung cancer [17,18], prostate cancer [19,20]. In colorectal cancer cells, overexpression of ILK promoted proliferation, metastasis, and invasion ability.…”

Section: Discussionmentioning

confidence: 99%

“…It has dual effects in the process of carcinogenesis, progression and metastasis. Firstly, ILK regulates multiple signal transduction pathways, including AKT, GSK-3β, Nf-κB, Erk and β-catenin signaling pathway [5][6][7][8][9]. Secondly, ILK forms a scaffold complex with some cytoskeleton proteins and plays a crucial role in regulating cell motility, cytoskeleton reorganization, focal adhesion, tumor progression and invasion [10].…”

Section: Ivyspringmentioning

confidence: 99%

Integrin-Linked Kinase Is Involved In the Proliferation and Invasion of Esophageal Squamous Cell Carcinoma

et al. 2020

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Esophageal squamous cell carcinoma (ESCC) is an aggressive type of cancer with high mortality rate in China, largely due to its high invasive and metastatic potential. The purposes of this study are to investigate the potential molecular mechanisms behind the aggressive nature of ESCC and search for new prognostic biomarkers. By employing the quantitative proteomic based strategy, we compared the proteomic profile between three ESCC samples and paired adjacent tissues. After bioinformatics analysis, four candidate proteins were validated in thirteen paired patient samples. Further validation of the key candidate, integrin-linked kinase (ILK), was carried out in one hundred patient samples. The specific inhibitor compound 22 (cpd22) was used to assess the influence of ILK to ESCC cell motility and invasiveness by applying wound-healing and transwell assay. Western blot analysis was performed to elucidate the signaling pathways involved in ILK-mediated ESCC invasion. Total 236 proteins were identified by proteomic analysis. Bioinformatics analysis suggested a key role of the collagen/integrin/ILK signaling pathway during ESCC progression. Further validation indicated that ILK is overexpressed in ESCC tissues and is correlated with poor patient prognosis. Inhibition of ILK kinase activity suppresses proliferation and blocks invasion and migration of ESCC cells. Signaling pathway analysis revealed that ILK regulates AKT phosphorylation on Ser473 but not GSK-3β on Ser9 to promote proliferation and motility of ESCC cells. In conclusion, our results indicated that ILK may play a crucial role in ESCC invasion and metastasis and may serve as a prognostic biomarker and therapeutic target for ESCC.

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Integrin-linked kinase overexpression promotes epithelial-mesenchymal transitionvianuclear factor-κB signaling in colorectal cancer cells

Abstract: ILK overexpression improved the proliferation, metastasis, and invasion ability of SW480 cells, and this effect may be mediated by the NF-κB signaling pathway.

Cited by 27 publications

References 30 publications

Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway

Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway

Emodin suppresses proliferation, migration and invasion in ovarian cancer cells by down regulating ILK in vitro and in vivo

Integrin-Linked Kinase Is Involved In the Proliferation and Invasion of Esophageal Squamous Cell Carcinoma

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