Proteomic analysis of ovarian cancer cells during epithelial-mesenchymal transition (EMT) induced by epidermal growth factor (EGF) reveals mechanisms of cell cycle control

Grassi, Mariana Lopes; Palma, Camila de Souza; Thomé, Carolina Hassibe; Lanfredi, Guilherme Pauperio; Poersch, Aline; Faça, Vítor Marcel

doi:10.1016/j.jprot.2016.06.009

Cited by 49 publications

(46 citation statements)

References 59 publications

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“…Convincing evidence suggests that the EMT has a close relationship with metastasis and invasion of malignant tumor [40][41][42]. In the current study, we found that expression of CUL4A is significantly associated with the EMT.…”

Section: Discussionsupporting

confidence: 65%

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

Liao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cullin 4A (CUL4A) is vital in cell survival, development, growth and cell cycle, it plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of CUL4A expression in colorectal cancer is unknown; in particular, the prognostic value of CUL4A combined with TP53 expression has not been explored. Methods: We analyzed the expression of CUL4A in both public database (Oncomine) and 180 cases of colorectal cancer and paired normal tissues by real-time polymerase chain reaction and western blotting. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of CUL4A in CRC proliferation and metastasis in vitro and in vivo. Markers of epithelial to mesenchymal transition (EMT) were evaluated by western blotting. Immunohistochemistry (IHC) was used to analyse the relationship between CUL4A expression and E-cadherin expression. Results: CUL4A and TP53 protein expression was significantly higher in cancerous tissues compared to normal tissues. Significant correlation between CUL4A and TP53 expression was observed. CUL4A expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Interestingly, patients with tumors that had both CUL4A overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P < 0.001). Multivariate analysis showed that patients with both CUL4A+ and TP53+ positive tumors had extremely poor OS and DFS. Knockdown of CUL4A by a short interfering RNA (siRNA) significantly suppressed the progression of EMT, proliferation, migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. ZEB1 silencing blocked CUL4A-driven these processes. Conclusion: CUL4A expression correlated positively with the prognosis of colorectal cancer. Mechanistically, ZEB1 was confirmed to mediate the function of CUL4A in regulating the EMT. The assessment of both CUL4A and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

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Section: Discussionsupporting

confidence: 65%

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

Liao

et al. 2018

Cell Physiol Biochem

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“…What is more, the mortality of EOC is directly related to the prevalence of metastatic diseases [21]. EMT is an important process that culminates with loss of epithelial traits and gain of mesenchymal traits [22].…”

Section: Discussionmentioning

confidence: 99%

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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“…A group of effectors triggering gynecological cancer development through the mTOR pathway can be identified as growth factors. Especially the epidermal growth factor receptor (EGFR) overexpression has been connected to a more aggressive tumor behavior [41]. Nishio et al [5] reported especially an important correlation of the EGFR overexpression with YB-1 expression in cervical cancer.…”

Section: Growth Factors In Mtor Dysregulationmentioning

confidence: 99%

The Communication between the PI3K/AKT/mTOR Pathway and Y-Box Binding Protein-1 in Gynecological Cancer

Sobočan

Bračič

Knez

et al. 2020

Cancers

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Studies of the mechanistic (mammalian) target of rapamycin inhibitors (mTOR) represent a step towards the targeted treatment of gynecological cancers. It has been shown that women with increased levels of mTOR signaling pathway targets have worse prognosis compared to women with normal mTOR levels. Yet, targeting mTOR alone has led to unsatisfactory outcomes in gynecological cancer. The aim of our review was therefore to provide an overview of the most recent clinical results and basic findings on the interplay of mTOR signaling and cold shock proteins in gynecological malignancies. Due to their oncogenic activity, there are promising data showing that mTOR and Y-box-protein 1 (YB-1) dual targeting improves the inhibition of carcinogenic activity. Although several components differentially expressed in patients with ovarian, endometrial, and cervical cancer of the mTOR were identified, there are only a few investigated downstream actors in gynecological cancer connecting them with YB-1. Our analysis shows that YB-1 is an important player impacting AKT as well as the downstream actors interacting with mTOR such as epidermal growth factor receptor (EGFR), Snail or E-cadherin.

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Proteomic analysis of ovarian cancer cells during epithelial-mesenchymal transition (EMT) induced by epidermal growth factor (EGF) reveals mechanisms of cell cycle control

Cited by 49 publications

References 59 publications

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

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

The Communication between the PI3K/AKT/mTOR Pathway and Y-Box Binding Protein-1 in Gynecological Cancer

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