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Emt cancer initiation

Jinlong Chen, Fufeng Gao, Naifu Liu
Identification of novel factors critical for epithelial to mesenchymal transition (EMT) and cancer initiating cell (CIC) formation may aid in the identification of novel therapeutics for the treatment of endometrial cancer. The present study demonstrated that L1 cell adhesion molecule (CAM) is critical for EMT and formation of CICs in endometrial cancer. Overexpression of L1CAM may promote EMT with increased formation of CICs in HEC-1A endometrial cancer cells. CICs and mesenchymal status resist chemotherapeutic drugs and may regenerate the various cell types in tumors, thereby resulting in relapse of the disease...
March 2018: Experimental and Therapeutic Medicine
Hyunkyoung Lee, Min Jung Pyo, Seong Kyeong Bae, Yunwi Heo, Indu Choudhary, Duhyeon Hwang, Hyeryeon Yang, Je-Hein Kim, Jinho Chae, Chang Hoon Han, Changkeun Kang, Seungshic Yum, Euikyung Kim
Epithelial-mesenchymal transition (EMT) is a key initial step in metastasis for malignant cancer cells to obtain invasive and motile properties. Inhibiting EMT has become a new strategy for cancer therapy. In our previous in vivo study, Nemopilema nomurai jellyfish venom (NnV) -treated HepG2 xenograft mice group showed that E-cadherin expression was strongly detected compared with non-treated groups. Therefore, this study aimed to determine whether NnV could inhibit the invasive and migratory abilities of HepG2 human hepatocellular carcinoma cells and to examine its effect on EMT...
February 12, 2018: Scientific Reports
Jihong Feng, Dalong Song, SiYuan Jiang, XiaoHui Yang, TingTing Ding, Hong Zhang, Junmin Luo, Jun Liao, Qian Yin
Emerging evidence has indicated that transforming growth factor-beta 1 (TGF-β1) induces the epithelial-mesenchymal transition (EMT) in cancer cells, thus promoting their motility and invasiveness. Quercetin, a member of the polyphenolic flavonoid family, has been reported to display anticancer activity against a broad range of cancer cell types. Indeed, numerous studies have shown the cancer preventive effects and molecular mechanisms of quercetin in vitro using diverse cell model systems. However, the potential effect of quercetin on EMT remains unclear...
February 6, 2018: Biochemical and Biophysical Research Communications
Kyra Campbell, Gaëlle Lebreton, Xavier Franch-Marro, Jordi Casanova
Several transcription factors have been identified that activate an epithelial-to-mesenchymal transition (EMT), which endows cells with the capacity to break through basement membranes and migrate away from their site of origin. A key program in development, in recent years it has been shown to be a crucial driver of tumour invasion and metastasis. However, several of these EMT-inducing transcription factors are often expressed long before the initiation of the invasion-metastasis cascade as well as in non-invasive tumours...
February 8, 2018: PLoS Genetics
Si Li, Fangying Xu, Jing Zhang, Lili Wang, Yang Zheng, Xuesong Wu, Jing Wang, Qiong Huang, Maode Lai
The immune contexture, a composition of the tumor microenvironment, plays multiple important roles in cancer stem cell (CSC) and epithelial-mesenchymal transition (EMT), and hence critically influences tumor initiation, progression and patient outcome. Tumor-associated macrophages (TAMs) are abundant in immune contexture, however their roles in CSC, EMT and prognosis of colorectal cancer (CRC) have not been elucidated. In 419 colorectal carcinomas, immune cell types (CD68+ macrophages, CD3+, CD4+ or CD8+ T lymphocytes, CD20+ B lymphocytes), EMT markers (E-cadherin and Snail) as well as the stem cell marker (CD44v6) were detected in tumor center (TC) and tumor invasive front (TF) respectively by immunohistochemistry...
2018: Oncoimmunology
Wei Xu, Hao Liu, Zhi-Gang Liu, Hong-Sheng Wang, Fan Zhang, Hao Wang, Ji Zhang, Jing-Jing Chen, Hong-Jun Huang, Yuan Tan, Meng-Ting Cao, Jun Du, Qiu-Gui Zhang, Guan-Min Jiang
Hepatocellular carcinoma (HCC) remains the third most common cause of cancer-related mortality. Resection and transplantation are the only curative treatments available, but are greatly hampered by high recurrence rates. Histone deacetylase inhibitors (HDACIs) are considered to be promising anticancer agents in drug development. Currently, four HDACIs have been granted Food and Drug Administration (FDA) approval for cancer. HDACIs have shown significant efficacy in hematological malignancies. However, they have limited effects in epithelial cell-derived cancers, including HCC, and the mechanisms of these are not elucidated...
January 30, 2018: Cancer Letters
Ling Lu, Jia Chen, Manli Li, Ling Tang, Rui Wu, Longtao Jin, Zhaofeng Liang
Tobacco smoke is one of the serious risk factors of gastric cancer. Epithelial‑mesenchymal transition (EMT) has been shown to be associated with the initiation and carcinogenesis of gastric cancer. The role of Notch pathway in regulating tobacco smoke-induced EMT has not been investigated. β‑carotene, a carotenoid present in fruits, vegetables and rice, suppresses cancer progression. In this investigation, we evaluated the regulatory role of Notch pathway in tobacco smoke‑mediated gastric EMT and the preventive effect of β‑carotene using a BALB/c mouse smoking model...
February 2, 2018: Oncology Reports
Xinxin Tian, Fangfang Tao, Baotong Zhang, Jin-Tang Dong, Zhiqian Zhang
Dysregulation of microRNA expression plays a pivotal role in the initiation and progression of a variety of human carcinomas including prostate cancer. Our previous studies have demonstrated that the silence of miR-203 contributes to the invasiveness of malignant breast cancer cells by targeting SNAI2. However, the effects and underlying mechanisms of miR-203/SNAI2 axis in prostate cancer have not been elucidated. The aim of this study is to explore the effects of miR-203/SNAI2 axis on the biological characteristics of prostate carcinomas both in vitro and in vivo...
February 1, 2018: IUBMB Life
Xing-Guang Wang, Na-Xin Yuan, Xin-Peng Li, Fang-Fang Chen
Cancer initiating cell (CIC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in lung cancer cell invasion and metastasis. They have been shown to occur in gefitinib resistance. Studying the molecular mechanisms of CICs, EMT and acquired gefitinib resistance will enhance the understanding of the pathogenesis and progression of the disease and offer novel targets for effective therapies. TWIK-related acid-sensitive K(+) (TASK-1) is expressed in a subset of non-small-cell lung cancer (NSCLC) cell lines, where it promotes cell proliferation while inhibiting apoptosis...
January 2018: Experimental and Therapeutic Medicine
Terese Karlsson, Reshma Sundar, Anders Widmark, Maréne Landström, Emma Persson
BACKGROUND: Transforming growth factor β (TGFβ) functions as a double-edged sword in prostate cancer tumorigenesis. In initial stages of the disease, TGFβ acts as a growth inhibitor upon tumor cells, whereas it in later stages of disease rather promotes invasion and metastatic potential. One well-known cellular source of TGFβ in the bone metastatic site is the bone-forming osteoblasts. Here we have studied the effects by osteoblast-derived factors on metastatic potential in several human prostate cancer cell lines...
January 31, 2018: Prostate
Chaolin Huang, Yuanhong Chen, Hang Liu, Jing Yang, Xuejing Song, Junping Zhao, Na He, Chengji J Zhou, Yongping Wang, Changjiang Huang, Qiaoxiang Dong
Pharmacological targeting of breast cancer stem cells (CSCs) is highly promising for the treatment of breast cancer, as the small population of CSCs is responsible for tumor initiation, progression, recurrence and chemo-resistance. Celecoxib is one of the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), which have chemo-preventive activity against cancers, including breast cancer and colorectal cancer. However, the mechanisms by which NSAIDs exert its cancer prevention effects have yet been completely understood...
December 29, 2017: Oncotarget
Ha Zhu, Yan Gu, Yiquan Xue, Ming Yuan, Xuetao Cao, Qiuyan Liu
Although myeloid-derived suppressor cells (MDSCs) have been demonstrated to contribute to tumor initiation, progression and metastasis, however, which MDSC subsets are preferentially expanded and activated, and what's the key molecular mechanism responsible for specific MDSC subsets in promoting tumor progression need to be fully addressed. Here we identify that Ly6GmiLy6CloCD11b+CXCR2+ subpopulation (named CXCR2+ MDSCs) are predominately expanded and recruited in systemic and local tumor microenvironment during breast cancer progression and metastasis...
December 29, 2017: Oncotarget
Yong-An Lee, Jong-Jin Kim, Jungyeol Lee, Jia Hui Jane Lee, Srikanta Sahu, Haw-Young Kwon, Sung-Jin Park, Se-Young Jang, Jun-Seok Lee, Zhenxun Wang, Wai Leong Tam, Bing Lim, Nam-Young Kang, Young-Tae Chang
Tumor initiating cells (TICs) have been alleged in clinical relapse and metastasis of a variety of epithelial cancers including lung cancer. While efforts for development of probes specific to TIC detection and targeting are ongoing, a universal TIC probe has yet to be developed. Here we report the first TIC-specific fluorescent chemical probe, TiY, with the identification of the molecular target as vimentin, a marker for epithelial-to-mesenchymal transition (EMT). TiY selectively stains TIC over differentiated tumor cells or normal cells, and facilitates the visualization and enrichment of functionally active TICs from patient derived tumor...
January 26, 2018: Angewandte Chemie
Susan Heavey, Paul Dowling, Gillian Moore, Martin P Barr, Niamh Kelly, Stephen G Maher, Sinead Cuffe, Stephen P Finn, Kenneth J O'Byrne, Kathy Gately
The PI3K-mTOR pathway is involved in regulating all hallmarks of cancer, and is often dysregulated in NSCLC, making it an attractive therapeutic target in this setting. Acquired resistance to PI3K-mTOR inhibition is a major hurdle to overcome in the success of PI3K-mTOR targeted agents. H460, A549, and H1975 resistant cells were generated by prolonged treatment in culture with Apitolisib (GDC-0980), a dual PI3K-mTOR inhibitor over a period of several months, from age-matched parent cells. Resistance was deemed to have developed when a log fold difference in IC50 had been achieved...
January 26, 2018: Scientific Reports
Ting Sun, Lin Jiao, Yangxia Wang, Yan Yu, Liang Ming
Melanoma is highly metastatic, and understanding of its molecular mechanism is urgently needed for the development of therapeutic targets and prognostic assessment for metastatic melanoma. SIRT1 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, belonging to the mammalian sirtuin family. It has been reported that SIRT1 is associated with metastasis in various cancers. However, the molecular mechanism of SIRT1 in melanoma metastasis remains to be clarified. Here we report that SIRT1 induces the epithelial-mesenchymal transition (EMT) by accelerating E-cadherin degradation via autophagy and facilitates melanoma metastasis...
January 26, 2018: Cell Death & Disease
Heather K Schofield, Jörg Zeller, Carlos Espinoza, Christopher J Halbrook, Annachiara Del Vecchio, Brian Magnuson, Tania Fabo, Ayse Ece Cali Daylan, Ilya Kovalenko, Ho-Joon Lee, Wei Yan, Ying Feng, Saadia A Karim, Daniel M Kremer, Chandan Kumar-Sinha, Costas A Lyssiotis, Mats Ljungman, Jennifer P Morton, Stefanie Galbán, Eric R Fearon, Marina Pasca di Magliano
Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras...
January 25, 2018: JCI Insight
Mai N Tran, Celina G Kleer
Located at 6q22-23, Ccn6 (WISP3) encodes for a matrix-associated protein of the CCN family, characterized by regulatory, rather than structural, roles in development and cancer. CCN6, the least studied member of the CCN family, shares the conserved multimodular structure of CCN proteins, as well as their tissue and cell-type specific functions. In the breast, CCN6 is a critical regulator of epithelial-to-mesenchymal transitions (EMT) and tumor initiating cells. Studies using human breast cancer tissue samples demonstrated that CCN6 messenger RNA and protein are expressed in normal breast epithelia but reduced or lost in aggressive breast cancer phenotypes, especially inflammatory breast cancer and metaplastic carcinomas...
January 22, 2018: Journal of Cell Communication and Signaling
Daniel P Hollern, Matthew R Swiatnicki, Eran R Andrechek
Human breast cancer has been characterized by extensive transcriptional heterogeneity, with dominant patterns reflected in the intrinsic subtypes. Mouse models of breast cancer also have heterogeneous transcriptomes and we noted that specific histological subtypes were associated with particular subsets. We hypothesized that unique sets of genes define each tumor histological type across mouse models of breast cancer. Using mouse models that contained both gene expression data and expert pathologist classification of tumor histology on a sample by sample basis, we predicted and validated gene expression signatures for Papillary, EMT, Microacinar and other histological subtypes...
January 2018: PLoS Genetics
Zhen Wang, Wei Wang, Kangrong Huang, Yueling Wang, Jing Li, Xinyuan Yang
MicroRNAs (miRNAs) are small non-coding RNAs composed of 18-25 nucleotides that regulate the expression of approximately 30% of human protein coding genes. Dysregulation of miRNAs plays a pivotal role in the initiation and progression of malignancies. Our study has shown that microRNA-34a (miR-34a) was upregulated in human endometrial cancer stem cells (ECSCs). However, it is unknown how miR-34a regulates endometrial cancer itself. Here, we report that miR-34a directly and functionally targeted Notch1. MiR-34a inhibited the proliferation, migration, invasion, EMT-associated phenotypes by downregulating Notch1 in endometrial cancer cells...
December 19, 2017: Oncotarget
Tsatsral Iderzorig, Joseph Kellen, Chike Osude, Sanjana Singh, James A Woodman, Christian Garcia, Neelu Puri
In the United States, lung cancer is the second most common cancer in men and women. In 2017, 222,500 new cases and 155,870 deaths from lung cancer are estimated to have occurred. A tyrosine kinase receptor, epidermal growth factor receptor (EGFR) is over expressed or mutated in non-small cell lung cancer (NSCLC) resulting in increased cell proliferation and survival. Tyrosine kinase inhibitors (TKIs) are currently being used as therapy for NSCLC patients, however, they have limited efficacy in NSCLC patients due to acquisition of resistance...
January 11, 2018: Biochemical and Biophysical Research Communications
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