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Objectives
The epithelial-mesenchymal-transition (EMT) is an important step in the invasion and metastasis of cancer. A critical molecular feature of this process is the downregulation of the E-cadherin expression, which is primarily controlled by Snail-related zinc-finger transcription factors. The aim of this study was to evaluate the prognostic...
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Context 1
... examples of immunohistochemically stained sections are shown in Figure 1. The results are shown in Table 1. A reduced E-cadherin expression was observed in 36.8% of the primary tumors. ...
Context 2
... addition, the vimentin expression was detected in only 5.2% of the primary tumors, with no substantial differences in clinical relevance or prognostic impact. Therefore, we be- lieve that the Slug and vimentin expression levels should be excluded as markers of the EMT status in the current study (Additional file 1: Table S1 and Additional file 2: Table S2). ...
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... Metastasis of early-stage cancer via lymph nodes or blood pathways may result in a poor long-term prognosis for cancer patients, thereby increasing the economic burden on people all over the world. [35][36][37][38][39] The rate of early metastasis in cancer patients has a significant impact on their treatment and prognosis. Numerous studies have confirmed that PAQR3 inhibits tumor metastasis and may improve the long-term prognosis of cancer patients ( Table 2). ...
Cancer was one of the common causes of death in the world, and it was increasing year by year. At present, Progestin and AdipoQ receptor family member 3 (PAQR3) was widely studied in cancer. It has been found that PAQR3 was down regulated in various cancers, such as the gastric cancer, osteosarcoma, glioma, hepatocellular carcinoma, acute lymphoblastic leukemia, laryngeal squamous cell carcinoma, esophageal cancer, breast cancer, non-small cell lung cancer, and colorectal cancer. The decreased expression of PAQR3 was associated with short overall survival and disease-free survival in patients with gastric cancer, hepatocellular carcinoma, laryngeal squamous cell carcinoma, esophageal cancer, breast cancer, and non-small cell lung cancer. PAQR3 could inhibit cancer progression by using the Ras/Raf/MEK/ERK, PI3/AKT, EMT and other mechanisms, and was negatively regulated by the miR-543, miR-15b-5p and miR-15b. The roles and signaling mechanisms of PAQR3, and the relationship between the expression of PAQR3 and prognosis in cancer progression are reviewed in this article, and provides new tumor marker and idea to guide cancer treatment.
... Since EMP represents a transition from epithelial to mesenchymal morphology of tumor cells, reduced immunohistochemical expression (negative, weak and moderate expression) of epithelial markers such as Ecadherin is counted as a positive EMP status of the studied tumor (8). The decrease in E-cadherin expression can only occur in groups of cells that represent specific branches in the tumor with different adhesive properties. ...
Ovarian cancer is the deadliest of gynecological malignancies, and despite the efforts to improve existing
treatment methods and early diagnosis, no progress has been made. Endometrial carcinoma (EC) is the fourth most
common malignancy in women.
The p53 gene has a leading role in the control of the cell cycle and the initiation of carcinogenesis. The p53
protein induces apoptosis, or cell cycle arrest, which allows the cell to repair genomic damage. Loss of p53 func
tion plays a central role in the development of malignant tumors. P53 is a tumor suppressor gene whose expression
in tumors is associated with progression and poor prognosis.
Ki67 protein is a cell proliferation marker. Immunohistochemical staining with Ki-67 provides reliable data
on the growth fraction of tumors. The Ki67 marker reflects cell proliferation in the tissue being examined. By
reading the immunohistochemical expression of Ki67, we can obtain information about the proliferative index and
about the growth fraction of tumors. The number of Ki67 positive tumor cells often correlates with the clinical
course.
... It is well known that ovarian cancer cells are prone to metastasis; in this process, epithelial-to-mesenchymal transition (EMT) is a necessary step during detachment of tumor cells from the primary tumor site and attachment to metastatic sites [35]. To ascertain the role of SLFN5 in migration, we observed that knockdown of SLFN5 in OVCAR3、HO-8910 and SKOV3 cells inhibited the migration of ovarian cancer cells, as assessed by scratch-wound assay. ...
Ovarian cancer is a disease with increasing incidence worldwide, and there is an urgent need for chemotherapy and biological targeted therapy. Epithelial-mesenchymal transformation (EMT) is an important initiation stage for tumor cells to acquire the ability to invade and metastasize. A growing number of findings suggest that human Schlafen family member 5(SLFN5) plays a key role in malignancy. However, the role of SLFN5 in ovarian cancer cells has not been fully elucidated. Samples were collected from patients with ovarian cancer diagnosed in Hangzhou First People's Hospital, and the expression of SLFN5 was detected by fluorescence quantitative PCR. The relationship between SLFN5 expression and the progression and malignancy of ovarian cancer was analyzed by using the expression profile data from the Cancer Genome Atlas (TCGA) database. The mRNA expression levels of SLFN5 related upstream and downstream signaling pathways were studied by fluorescence quantitative PCR. Silencing SLFN5 was performed by siRNA transfection. The expression of SLFN5 and transfer-related proteins was examined by Western blot. Transwell and wound healing experiments investigated the migration and invasion ability of ovarian cancer cells. TCGA database analysis results showed that in the population with high SLFN5 expression, compared with the group with low SLFN5 expression, OS was worse (P = 0.011). SLFN5 silencing had a significant inhibitory effect on EMT and invasion movement of ovarian cancer cells. RT-PCR method was used to detect the mRNA changes of SLFN5 in ovarian cancer tissue and adjacent tissue. It was found that the expression of SLFN5 in ovarian cancer tissue was increased, with a significant difference (P < 0.05). Together, these results suggest that SLFN5 may play a synergistic role in tumorigenesis and development of ovarian cancer cells, providing a potential target for future drug development for the treatment of ovarian cancer.
... METTL3 has also been found to promote EMT by up-regulating receiver tyrosine kinase AXL. Multiple studies have linked EMT to OC cell invasion and metastasis [133][134][135]. By promoting AXL translation and EMT, it is assumed that METTL3 plays a crucial carcinogenic role in the formation and/or invasion of OC. ...
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Abstract
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... Metastasis is the most important step in tumor progression. Metastasis to the lymph node or blood can lead to poor long-term prognosis of patients with early-stage cancer (Takai et al. 2014;Yan et al. 2019;Cao et al. 2020;Yi et al. 2018). Increasing or decreasing the expression of lncRNAs could inhibit the growth and migration of cancer (Zhang et al. 2020;Shang et al. 2019;Parolia et al. 2019;Wang et al. 2019), which can be employed to reduce the rate of early metastasis and improve the treatment and prognosis of cancer patients. ...
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Abbreviations: CRLS1, cardiolipin synthase 1; EMT, epithelial–mesenchymal transformation; HCC, hepatocellular carcinoma; LncRNA, long non-coding RNA; LUAD, lung adenocarcinoma; NSCLC, non-small cell lung cancer; OSCC, oral squamous cell carcinoma; PCAN, proliferating cell nuclear antigen; PTEN, phosphatase and tensin homologue; RCC, renal cell carcinoma; SPAR, small regulatory polypeptide of amino acid response; TSCC, tongue squamous cell carcinoma; VSMCs, vascular smooth muscle cell.
... Ovarian cancers with mesenchymal signature are known to have worse overall survival [47]. Immunohistological analyses of both primary and metastatic ovarian carcinoma also show that mesenchymal markers are accompanied with peritoneal dissemination and poor survival of ovarian cancer patients [48,49]. Consistent with these findings, we previously found that mesenchymal-like but not epithelial-like ovarian cancer cell lines were able to undergo robust intraperitoneal tumor development [31]. ...
Fibroblast activation protein (FAP) is tumor-specific and plays an important role in tumorigenecity. However, agents against its enzymatic activity or extracellular presence were unsuccessful in the clinic for undefined reasons. Here we show that FAP expression is higher in advanced ovarian cancer and is only detected in invasive ovarian cancer cells. Silencing FAP induces apoptosis and FAP’s enzymatic activity is dispensable for cell survival. To elucidate the cause of apoptosis, we find that NF-κB activity is diminished when FAP is depleted and BIRC5 (survivin) acts downstream of FAP-NF-κB axis to promote cell survival. To uncover the link between FAP and NF-κB activation, we reveal that PRKDC (DNA-PK, DNA-dependent protein kinase) forms complex with FAP and is required for NF-κB activation and cell survival. Remarkably, FAP-PRKDC interaction occurs only in lipid rafts, and depleting FAP prevents lipid raft localization of PRKDC. Given the known ability of PRKDC to direct NF-κB activation, these results suggest that FAP recruits PRKDC in lipid rafts for NF-κB activation. FAP’s non-enzymatic role and functioning from lipid rafts for cell survival also offer an explanation on the failure of past FAP-targeted therapies. Finally, we demonstrate that EpCAM aptamer-delivered FAP siRNA impeded intraperitoneal xenograft development of ovary tumors.
... This leads to activation of EMT transcription factors such as Snail, Slug, Twist, and Zeb1/2 to promote the down-regulation of epithelialrelated genes such as E-cadherin (E-cad) and, in parallel, enhancement of the expression of mesenchymal-related genes such as vimentin (8,11,12). EMT is a critical step in the progression of cancer in many (albeit not all) tissues, including epithelial ovarian cancer (13), where induction of EMT (through up-regulation of Snail, Twist, and Zeb1/2) is associated with poor overall survival of patients (14). Therefore, finding ways to inhibit the EMT process and promote the differentiation in ovarian cancer cells represents a possible therapeutic strategy to improve ovarian cancer patient survival. ...
Epithelial–mesenchymal transition (EMT) is a cellular mechanism used by cancer cells to acquire migratory and stemness properties. In this study, we show, through in vitro, in vivo, and 3D culture experiments, that the mitochondrial protein LACTB manifests tumor suppressor properties in ovarian cancer. We show that LACTB is significantly down-regulated in epithelial ovarian cancer cells and clinical tissues. Re-expression of LACTB negatively effects the growth of cancer cells but not of non-tumorigenic cells. Mechanistically, we show that LACTB leads to differentiation of ovarian cancer cells and loss of their stemness properties, which is achieved through the inhibition of the EMT program and the LACTB-dependent down-regulation of Snail2/Slug transcription factor. This study uncovers a novel role of LACTB in ovarian cancer and proposes new ways of counteracting the oncogenic EMT program in this model system.
... EMT is an important process in cancer invasion and metastasis and involves more than 30 gene expressions [49]. Cell morphology and cell-cell adhesion also affect invasion and migration [50,51]. NF-κB is also associated with decreased survival rate in ovarian cancer [23]. ...
Ovarian cancer is one of the most lethal gynecological cancers, and 80% are high-grade serous carcinomas (HGSOC). Despite advances in chemotherapy and the development of targeted therapies, the survival rate of HGSOC has only moderately improved. Therefore, a cell model that reflects the pathogenesis and clinical characteristics of this disease is urgently needed. We previously developed a human fallopian tube epithelial cell line (FE25) with p53 and Rb deficiencies. After long-term culture in vitro, cells at high-passage numbers showed spontaneous transformation (FE25L). This study aimed to compare FE25 cells cultured in vitro for low (passage 16–31) and high passages (passage 116–139) to determine whether these cells can serve as an ideal cell model of HGSOC. Compared to the cells at low passage, FE25L cells showed increased cell proliferation, clonogenicity, polyploidy, aneuploidy, cell migration, and invasion. They also showed more resistance to chemotherapy and the ability to grow tumors in xenografts. RNA-seq data also showed upregulation of hypoxia, epithelial-mesenchymal transition (EMT), and the NF-κB pathway in FE25L compared to FE25 cells. qRT-PCR confirmed the upregulation of EMT, cytokines, NF-κB, c-Myc, and the Wnt/β-catenin pathway. Cross-platform comparability found that FE25L cells could be grouped with the other most likely HGSOC lines, such as TYKNU and COV362. In conclusion, FE25L cells showed more aggressive malignant behavior than FE25 cells and hence might serve as a more suitable model for HGSOC research.
... Moreover, cells presenting a higher expression of the epithelial to mesenchymal transition usually also associate a higher level of vimentin, and therefore, a higher risk to develop chemotherapy resistance. In this respect, studies published so far demonstrated that cases in which the epithelial to mesenchymal transition was present reported poorer long-term outcomes expressed through a lower cancer related survival [13][14][15]. ...
In the last decades understanding the relationship between the circulating platelets and the biological aggressivity of ovarian cancer gave the opportunity to researchers to introduce new therapeutic lines in ovarian cancer patients with promising results. Therefore, this subject has become intensively studied and surprising correlation ships have been observed. One of the most recently investigated issues regards the influence of circulating platelets on epithelial ovarian cancer refers to the platelets’ ability to induce the epithelial to mesenchymal transition. The current paper aims to discuss about this subject and about the clinical implications of the process.
... 5 EMT-positive status has been correlated with poor progression free survival and overall survival. 6 Furthermore, in metastatic serous ovarian carcinoma effusions, several proteins related to EMT, including vimentin and ZEB1, have been found to be markers of a poor chemotherapy response. 7 Recent studies have highlighted a link between EMT and the properties of cancer stem cells (CSCs). ...
NANOG engages with tumour initiation and metastasis by regulating the epithelial–mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). However, its role in association with pAMPKα, and its clinical significance in EOC have not been elucidated even though AMPK is known to degrade NANOG in various human cancers. Hence, we investigated the role of pAMPKα and its association with NANOG as potential prognostic biomarkers in EOC. Both NANOG and pAMPKα expression were significantly overexpressed in EOCs comparing nonadjacent normal epithelial tissues, benign tissues, and borderline tumours. NANOG overexpression was significantly associated with poor disease‐free survival (DFS) and overall survival (OS), whereas pAMPKα overexpression was associated with good DFS and OS. Importantly, multivariate analysis revealed that the combination of high NANOG and low pAMPKα expression was a poor independent prognostic factor for DFS and was associated with platinum resistance. In ovarian cancer cell lines, siRNA‐mediated NANOG knockdown diminished migration and invasion properties by regulating the EMT process via the AMPK/mTOR signalling pathway. Furthermore, treatment with AMPK activator suppressed expression of stemness factors such as NANOG, Oct4 and Sox2. Collectively, these findings established that the combination of high NANOG and low pAMPKα expression was associated with EOC progression and platinum resistance, suggesting a potential prognostic biomarker for clinical management in EOC patients.
