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Emt cancer initiation

Rui Feng, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Syuichi Iwahashi, Yu Saito, Mitsuo Shimada
Cancer-associated fibroblasts (CAFs), which derived from cancer tissues stroma, interact with cancer cells and play an important role in cancer initiation, growth and metastasis. Nab-paclitaxel (nab-PTX) is the 130nm albumin binding paclitaxel and recommended for many kinds of cancer chemotherapy. It has been reported that nab-PTX stromal disrupting effect during pancreatic cancer treatment. The aim of this study is to illustrate the role of nab-PTX in cancer cells and CAFs interaction. The cancer cells (Mia paca2 and Panc-1) were co-cultured with CAFs or treat with CAFs conditioned medium, then their migration and invasion ability, epithelial-mesenchymal transition (EMT) related markers expression and CXCL10 expression and secretion were detected...
June 14, 2018: Cancer Science
Chang Liu, Tatiana Shaurova, Suzanne Shoemaker, Martin Petkovich, Pamela A Hershberger, Yun Wu
Mutation in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene drives the development of lung cancer. EGFR tyrosine kinase inhibitors (EGFR TKI) including erlotinib and afatinib are initially effective in treating EGFR mutant non-small cell lung cancer (NSCLC). However, drug resistance quickly develops due to several mechanisms, including induction of the epithelial-mesenchymal transition (EMT). No effective therapies are currently available for patients who develop EMT-associated EGFR TKI resistance...
June 14, 2018: Molecular Pharmaceutics
Kai Zhou, Jun Rao, Zhi-Hua Zhou, Xiao-Hong Yao, Feng Wu, Jing Yang, Lang Yang, Xia Zhang, You-Hong Cui, Xiu-Wu Bian, Yu Shi, Yi-Fang Ping
Epithelial-mesenchymal transition (EMT) plays a critical role in initiating tumor invasion and metastasis of colorectal cancer (CRC), although the underlying mechanisms remain to be clarified. Herein, we demonstrate that the active form of Rac family small GTPase 1 (RAC1-GTP) is overexpressed in CRCs and promotes the EMT-mediated invasion of CRC cells through activation of the signal transducers and activators of transcription 3 (STAT3) pathway. Increased expression of RAC1-GTP in CRC tissues was positively correlated with the TNM stages of CRCs and indicated poor prognosis of CRC patients...
June 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Maud Debaugnies, Adriana Sánchez-Danés, Sandrine Rorive, Maylis Raphaël, Mélanie Liagre, Marie-Astrid Parent, Audrey Brisebarre, Isabelle Salmon, Cédric Blanpain
YAP and TAZ are key downstream regulators of the Hippo pathway, regulating cell proliferation and differentiation. YAP and TAZ activation has been reported in different cancer types. However, it remains unclear whether they are required for the initiation of major skin malignancies like basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Here, we analyze the expression of YAP and TAZ in these skin cancers and evaluate cancer initiation in knockout mouse models. We show that YAP and TAZ are nuclear and highly expressed in different BCC types in both human and mice...
June 6, 2018: EMBO Reports
James B McCarthy, Dorraya El-Ashry, Eva A Turley
This review summarizes the roles of CAFs in forming a "cancerized" fibrotic stroma favorable to tumor initiation and dissemination, in particular highlighting the functions of the extracellular matrix component hyaluronan (HA) in these processes. The structural complexity of the tumor and its host microenvironment is now well appreciated to be an important contributing factor to malignant progression and resistance-to-therapy. There are multiple components of this complexity, which include an extensive remodeling of the extracellular matrix (ECM) and associated biomechanical changes in tumor stroma...
2018: Frontiers in Cell and Developmental Biology
Qipeng Liu, Qiaqia Li, Sen Zhu, Yang Yi, Qi Cao
B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1), a core member of polycomb repressive complex 1 (PRC1), has been intensely investigated in the field of cancer epigenetics for decades. Widely known as a critical regulator in cellular physiology, BMI1 is essential in self-renewal and differentiation in different lineages of stem cells. BMI1 also plays a significant role in cancer etiology for its involvement in pathological progress such as epithelial-mesenchymal transition (EMT) and cancer stem cell maintenance, propagation, and differentiation...
June 1, 2018: Asian Journal of Andrology
Oğuzhan Karaosmanoğlu, Sreeparna Banerjee, Hülya Sivas
BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Complete epithelial to mesenchymal transition (EMT) has long been considered as a crucial step for metastasis initiation. It has, however, become apparent that many carcinoma cells can metastasize without complete loss of epithelial traits or with incomplete gain of mesenchymal traits, i.e., partial EMT. Here, we aimed to determine the similarities and differences between complete and partial EMT through over-expression of the EMT-associated transcription factor Slug in different HCC-derived cell lines...
June 1, 2018: Cellular Oncology (Dordrecht)
Sumie Kato, María Francisca Liberona, Javier Cerda-Infante, Marianela Sanchez, Jenny F Henriquez, Carolina Bizama, Maria Loreto Bravo, Pamela Gonzalez, Roger Gejman, Jorge Branes, Karen García, Carolina Ibañez, Gareth Ivor Owen, Juan Carlos Roa, Viviana Montecinos, Mauricio Arturo Cuello
Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, allowing metastasis and cancer progression. Here, we studied whether simvastatin, a lipophilic statin, could impair the metastatic potential of CICs in high-grade serous ovarian cancer (HGS-ovC), the most lethal among the gynecologic malignancies. qPCR, immunoblotting, and immunohistochemistry were used to assess simvastatin effects on proteins involved in stemness and epithelial-mesenchymal cell plasticity (EMT). Its effects on tumor growth and metastasis were evaluated using different models (e...
May 30, 2018: Endocrine-related Cancer
Ulrich Andergassen, Kristina Schlenk, Udo Jeschke, Harald Sommer, Alexandra Kölbl
The primary cause of breast cancer‑associated mortality is the formation of distant metastasis. During the metastatic process, single tumor cells dissolve from the primary tumor site and undergo various changes in cell adhesion and motility properties. The tumor cells invade the blood stream and travel to different sites of the body, where they may initiate outgrowth. These cells are referred to as circulating tumor cells (CTCs). The process of changing cellular properties is known as epithelial to mesenchymal transition (EMT)...
May 29, 2018: Molecular Medicine Reports
Ran Gao, Guoqing Lv, Cuicui Zhang, Xiaoli Wang, Lijing Chen
Medulloblastoma is the most common malignant brain tumor in children. Despite remarkable advances over previous decades, the long-term survival of patients with medulloblastoma remains poor due to the frequent metastatic nature of this malignancy. The aim of the present study was to examine the role of tripartite motif containing 59 (TRIM59) in cell metastasis in medulloblastoma. It was initially demonstrated that TRIM59 expression was significantly increased in clinical medulloblastoma tissues compared with adjacent non-cancerous tissues and differentially expressed in a series of medulloblastoma cell lines...
June 2018: Oncology Letters
Fanghua Qi, Jinjing Wang, Lin Zhao, Pingping Cai, Wei Tang, Zhixue Wang
Cinobufacini, an aqueous extract from the skins and parotid venom glands of the toad Bufo bufo gargarizans Cantor, is a well known traditional Chinese medicine widely used in clinical cancer therapy in China. Its therapeutic effect is especially pronounced in liver cancer. However, the precise mechanisms induced by cinobufacini in human hepatocellular carcinoma (HCC) cells are still not very clear. Here, we investigated the effects and mechanisms of cinobufacini on inhibiting HepG2 cells invasion and metastasis...
May 22, 2018: Bioscience Trends
Margherita Sisto, Sabrina Lisi, Domenico Ribatti
The link between inflammatory microenvironment and cancer emerged in the last years as a decisive factor in the induction of the pathological epithelial-mesenchymal transition (EMT). The EMT induces changes of cell states converting the epithelial cells to mesenchymal cells when this program is fully executed and EMT has emerged as a central driver of tumor malignancy. Cellular pathways activated by chronic inflammation brought about by chronic infections, by immune-mediated diseases, or by dysregulated wound healing at sites of repetitive tissue injury, constitute risk factors or initial cell transformation and for cancer progression...
May 23, 2018: Histochemistry and Cell Biology
Yanbin Ma, Haofeng Zhang, Chaoliang Xiong, Zheng Liu, Qingji Xu, Jing Feng, Jun Zhang, Zhaoqing Wang, Xiyun Yan
Cadherin switch is an initiating factor of epithelial-mesenchymal transition (EMT) and is intimately correlated with cancer metastatic potential; however, its underlying mechanisms remain unclear. Here, using a transforming growth factor-β (TGF-β)-induced EMT model, we provide explicit evidence that CD146, with elevated expression and activity in a variety of cancers, is a key factor involved in the cadherin switch. We show that CD146 can be induced by TGF-β signaling. Moreover, CD146 expression is positively correlated with the activation levels of STAT3/Twist and ERK pathways...
August 28, 2018: Cancer Letters
Huifeng Gu, Tianhe Huang, Yicheng Shen, Yin Liu, Fuling Zhou, Yanxia Jin, Haseeb Sattar, Yongchang Wei
Radioresistance is one of the primary causes responsible for therapeutic failure and recurrence of cancer. It is well documented that reactive oxygen species (ROS) contribute to the initiation and development of gastric cancer (GC), and the levels of ROS are significantly increased in patients with GC accompanied with abnormal expressions of multiple inflammatory factors. It is also well documented that ROS can activate cancer cells and inflammatory cells, stimulating the release of a variety of inflammatory cytokines, which subsequently mediates the tumor microenvironment (TME) and promotes cancer stem cell (CSC) maintenance as well as renewal and epithelial-mesenchymal transition (EMT), ultimately resulting in radioresistance and recurrence of GC...
2018: Oxidative Medicine and Cellular Longevity
Farhan S Cyprian, Halema F Al-Farsi, Semir Vranic, Saghir Akhtar, Ala-Eddin Al Moustafa
Oncoviruses are implicated in around 20% of all human cancers including both solid and non-solid malignancies. Epstein-Barr virus (EBV) and human papillomaviruses (HPVs) are the most common oncoviruses worldwide. Currently, it is well established that onco-proteins of EBV (LMP1, LMP2A, and EBNA1) and high-risk HPVs (E5 and E6/E7) play an important role in the initiation and/or progression of several human carcinomas, including cervical, oral, and breast. More significantly, it has been recently pointed out that viral onco-proteins of EBV and high-risk HPVs can be co-present and consequently cooperate to initiate and/or amplify epithelial-mesenchymal transition (EMT), which is the hallmark of cancer progression and metastasis...
2018: Frontiers in Oncology
Chen Li, Zhenfan Wang, Ninghan Feng, Jian Dong, Xiaoyan Deng, Yin Yue, Yuehong Guo, Jianquan Hou
Epithelial to mesenchymal transition (EMT) serves important roles in tumor invasion, metastasis, formation of cancer initiating cells (CICs) and drug resistance. HLA‑F adjacent transcript 10 (FAT10) has been proposed as an oncogene in bladder cancer. However, the functional contribution of FAT10 to EMT and the formation of CICs remains unclear in bladder cancer. The present study reports that FAT10 protein expression is upregulated in bladder cancer cell lines, and the overexpression of FAT10 promotes EMT and the formation of CICs in bladder cancer UMUC‑3 cells...
May 9, 2018: Molecular Medicine Reports
Vahid Bagheri, Bahram Memar, Ramezan Behzadi, Mohsen Aliakbarian, Ali Jangjoo, Mostafa Mehrabi Bahar, Samaneh Talebi, Mehran Gholamin, Mohammad R Abbaszadegan
Gastric cancer (GC) is the third and fifth cause of cancer-associated mortality for men and women throughout the world, respectively. Despite the use of surgery and chemotherapy for GC therapy, there are no efficient therapeutic protocols for it to date. Cancer stem cells (CSCs) due to their pivotal role in tumor initiation, growth, progression, invasion, distant metastasis, recurrence and resistance to anticancer drugs are very appealing targets for cancer therapies. Here, we isolated and identified CSCs from a chemotherapy-treated patient...
May 10, 2018: Journal of Cellular Physiology
Hong Shen, Ling Yin, Ganlu Deng, Cao Guo, Ying Han, Yiyi Li, Changjing Cai, Yaojie Fu, Shanshan Liu, Shan Zeng
Activation of autophagy significantly affects cancer cell behaviors, such as proliferation, differentiation, and invasiveness. Epithelial-to-mesenchymal transition (EMT) as an initial step of malignant transformation of cancer cells was linked to the activation of autophagy, but the detailed molecular mechanisms are still unknown. The present study investigates the effects of Beclin-1, a key molecule involved in activation of autophagy, on EMT of colon cancer cells. The normal colon epithelia cell line of CCD-18Co and six colon cancer cell lines with different expression levels of Beclin-1 were used in this study...
May 8, 2018: Journal of Cellular Biochemistry
Anne Grosse-Wilde, Rolf E Kuestner, Stephanie M Skelton, Ellie MacIntosh, Aymeric Fouquier d'Hérouël, Gökhan Ertaylan, Antonio Del Sol, Alexander Skupin, Sui Huang
According to the sequential metastasis model, aggressive mesenchymal (M) metastasis-initiating cells (MICs) are generated by an epithelial-mesenchymal transition (EMT) which eventually is reversed by a mesenchymal-epithelial transition (MET) and outgrowth of life-threatening epithelial (E) macrometastases. Paradoxically, in breast cancer M signatures are linked with more favorable outcomes than E signatures, and M cells are often dispensable for metastasis in mouse models. Here we present evidence at the cellular and patient level for the cooperation metastasis model, according to which E cells are MICs, while M cells merely support E cell persistence through cooperation...
April 13, 2018: Oncotarget
Varun Maturi, Anita Morén, Stefan Enroth, Carl-Henrik Heldin, Aristidis Moustakas
Transcriptional regulation mediated by the zinc finger protein Snail1 controls early embryogenesis. By binding to the epithelial tumor suppressor CDH1 gene, Snail1 initiates the epithelial-mesenchymal transition (EMT). The EMT generates stem-like cells and promotes invasiveness during cancer progression. Accordingly, Snail1 mRNA and protein is abundantly expressed in triple-negative breast cancers with enhanced metastatic potential and phenotypic signs of the EMT. Such high endogenous Snail1 protein levels permit quantitative chromatin immunoprecipitation-sequencing (ChIP-seq) analysis...
May 4, 2018: Molecular Oncology
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