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Jung Min Ha, Sung Ji Yun, Seo Yeon Jin, Hye Sun Lee, Sun Ja Kim, Hwa Kyoung Shin, Sun Sik Bae
Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that krüppel-like factor 8 (KLF8) is essential for tumor necrosis factor α (TNFα)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with TNFα significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by TNFα stimulation in an ERK-dependent manner...
January 2017: Korean Journal of Physiology & Pharmacology
Hae-Miru Lee, Kyung-A Hwang, Kyung-Chul Choi
Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that interfere with normal functions of natural hormones in the body, leading to a disruption of the endocrine system. Specifically, EDCs have the potential to cause formation of several hormone-dependent cancers, including breast, ovarian, and prostate cancers. Epithelial mesenchymal transition (EMT) process by which epithelial cells lose their cell polarity and cell-cell adhesion and acquire mesenchymal phenotype is closely associated with malignant transformation and the initiation of cancer metastasis...
December 29, 2016: Molecular and Cellular Endocrinology
Yutaro Otsuka, Hiroki Sato, Tsukasa Oikawa, Yasuhito Onodera, Jin-Min Nam, Ari Hashimoto, Kiyoshi Fukunaga, Kanako C Hatanaka, Yutaka Hatanaka, Yoshihiro Matsuno, Satoshi Fukuda, Hisataka Sabe
BACKGROUND: Squamous cell carcinoma of the tongue (tongue SCC) is a major subtype of head and neck squamous cell carcinoma (HNSCC), which is an intractable cancer under current therapeutics. ARF6 and its effector AMAP1 are often overexpressed in different types of cancers, such as breast cancer and renal cancer, and in these cancers, AMAP1 binds to EPB41L5 to promote invasion, metastasis, and drug resistance. EPB41L5 is a mesenchymal-specific protein, normally induced during epithelial-mesenchymal transition (EMT) to promote focal adhesion dynamics...
November 21, 2016: Cell Communication and Signaling: CCS
Lili Wang, Angela N Brooks, Jean Fan, Youzhong Wan, Rutendo Gambe, Shuqiang Li, Sarah Hergert, Shanye Yin, Samuel S Freeman, Joshua Z Levin, Lin Fan, Michael Seiler, Silvia Buonamici, Peter G Smith, Kevin F Chau, Carrie L Cibulskis, Wandi Zhang, Laura Z Rassenti, Emanuela M Ghia, Thomas J Kipps, Stacey Fernandes, Donald B Bloch, Dylan Kotliar, Dan A Landau, Sachet A Shukla, Jon C Aster, Robin Reed, David S DeLuca, Jennifer R Brown, Donna Neuberg, Gad Getz, Kenneth J Livak, Matthew M Meyerson, Peter V Kharchenko, Catherine J Wu
Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1...
November 14, 2016: Cancer Cell
Li-Fang Chu, Ning Leng, Jue Zhang, Zhonggang Hou, Daniel Mamott, David T Vereide, Jeea Choi, Christina Kendziorski, Ron Stewart, James A Thomson
BACKGROUND: Human pluripotent stem cells offer the best available model to study the underlying cellular and molecular mechanisms of human embryonic lineage specification. However, it is not fully understood how individual stem cells exit the pluripotent state and transition towards their respective progenitor states. RESULTS: Here, we analyze the transcriptomes of human embryonic stem cell-derived lineage-specific progenitors by single-cell RNA-sequencing (scRNA-seq)...
2016: Genome Biology
Yi-Nan Shen, Hai-Guan He, Yang Shi, Jian Cao, Jian-Yong Yuan, Zhou-Chong Wang, Chun-Feng Shi, Nan Zhu, Yong-Peng Wei, Fang Liu, Jia-Li Huang, Guang-Shun Yang, Jun-Hua Lu
Krüppel-like factor 8 (KLF8) is highly expressed in hepatocellular carcinoma (HCC) and contributes to tumor initiation and progression by promoting HCC cell proliferation and invasion. However, the role of KLF8 in liver cancer stem cells (LCSCs) is not known. In the current study, we investigated the role of KLF8 in LCSCs to determine if KLF8 is a novel marker of these cells. We found that KLF8 was highly expressed in primary HCC tumors, distant migrated tissues, and LCSCs. Patients with high KLF8 expression had a poor prognosis...
February 2017: Molecular Carcinogenesis
Satadru K Lahiri, Heng Lu, Debarati Mukherjee, Lin Yu, Jihe Zhao
Krüppel-like factor 8 (KLF8) plays important roles in cancer and is strictly regulated by various post-translational modifications such as sumoylation, acetylation, ubiquitylation and PARylation. Here we report a novel phosphorylation of KLF8 by ERK2 responsible and critical for the stability of KLF8 protein. The full-length KLF8 protein displays a doublet in SDS-PAGE gel. The upper band of the doublet, however, disappeared when the N-terminal 50 amino acids were deleted. In its full-length the upper band disappeared upon phosphatase treatment or mutation of the serine 48 (S48) to alanine whereas the lower band was lost when the S48 was mutated to aspartic acid that mimics phosphorylated S48...
2016: American Journal of Cancer Research
Guo Yu, Fei Wu, Ersong Wang
BACKGROUND/AIMS: The transcription factor Krüppel-like factor (KLF) 8 plays important roles in tumorigenesis and tumor metastasis. However, the relationship between KLF8 and glioma cell chemoresistance is not known. METHODS: The effects of KLF8 on glioma cell proliferation, apoptosis and chemosensitivity to temozolomide (TMZ) were analyzed by Cell Counting Kit 8 assay and flow cytometry assay. A xenograft model was used to study the effect of KLF8 on tumor growth and sensitivity to TMZ...
2016: Cellular Physiology and Biochemistry
Xiaoping Yi, Yixiong Li, Hongyan Zai, Xueying Long, Wenzheng Li
BACKGROUND: The transcription factor Krüppel-like factor 8 (KLF8) plays an important role in tumor development and growth, but its role in pancreatic cancer (PC) is not clear. METHODS: KLF8 expression in human PC cell lines and tumor tissues was measured by quantitative real-time polymerase chain reaction and Western blot analyses. The effects of lentivirus mediated knockdown of KLF8 on proliferation and growth in Panc-1 pancreatic cancer cells were examined. RESULTS: KLF8 was overexpressed in 5 pancreatic cancer cell lines and in samples from patients with PC...
July 1, 2016: Gene
Debarati Mukherjee, Heng Lu, Lin Yu, Chunjiang He, Satadru K Lahiri, Tianshu Li, Jihe Zhao
Krüppel-like factor 8 (KLF8) has been strongly implicated in breast cancer metastasis. However, the underlying mechanisms remain largely unknown. Here we report a novel signaling from KLF8 to C-X-C cytokine receptor type 4 (CXCR4) in breast cancer. Overexpression of KLF8 in MCF-10A cells induced CXCR4 expression at both mRNA and protein levels, as determined by quantitative real-time PCR and immunoblotting. This induction was well correlated with increased Boyden chamber migration, matrigel invasion and transendothelial migration (TEM) of the cells towards the ligand CXCL12...
April 26, 2016: Oncotarget
Qingqing Yan, Wenjing Zhang, Yao Wu, Meiyan Wu, Mengnan Zhang, Xinpeng Shi, Jinjun Zhao, Qingzhen Nan, Ye Chen, Long Wang, Tianming Cheng, Jiachu Li, Yang Bai, Side Liu, Jide Wang
The transcription factor Krüppel-like factor (KLF)8 plays an important role in the formation of several human tumors, including colorectal cancer. We recently identified four-and-a-half LIM protein 2 (FHL2) as a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which KLF8 affects FHL2-mediated tumor proliferation, EMT and metastasis remains unknown. Here, we showed that KLF8 overexpression promoted EMT and metastatic phenotypes. KLF8 expression was stimulated by transforming growth factor (TGF)-β1...
September 22, 2015: Oncotarget
Hongyang Shi, Yuqiang Ji, Dexin Zhang, Yun Liu, Ping Fang
Epithelial-mesenchymal transition (EMT) has been shown to be related to the pathogenesis of various diseases. Recently, microRNAs (miRNA) have been recognized as a new class of genes involved in human tumorigenesis. In this study, we found that the expression levels of miR-135a were dramatically decreased in NSCLC cell lines and clinical NSCLC tissue samples. Then, we demonstrated that miR-135a significantly suppressed the migration and invasion of lung cancer cells in vitro, suggesting that miR-135a may be a novel tumor suppressor...
September 11, 2015: Biochemical and Biophysical Research Communications
Yan Gao, Qing Cao, Lei Lu, Xuena Zhang, Zan Zhang, Xiaohua Dong, Wenshuang Jia, Ying Cao
BACKGROUND: Kruppel-like factors (Klfs) are a family of transcription factors consisting of 17 members in mammals, Klf1-Klf17, which are involved in fundamental cellular physiological procedures, such as cell proliferation, differentiation, and apoptosis. However, their functions in embryonic development have been poorly understood. Our previous study has demonstrated that the pluripotency factor Klf4 participates in germ layer formation and axis patterning of Xenopus embryos by means of the regulation of key developmental signals...
October 2015: Developmental Dynamics: An Official Publication of the American Association of Anatomists
Jing Wang, Jian Li Hu, Ru Bo Cao, Qian Ding, Gang Peng, Shi Jiang Fei, Yao Jiang, Peng Cheng Li, Kun Yu Yang, Wen Jie Zhang, Gang Wu, Ruo Zheng Wang, Pin Dong Li
The present study aimed to characterize the expression of Krüppel-like factor 8 (KLF8) in nasopahryngeal carcinoma (NPC) cell lines and determine its effect on tumor development and invasion following KLF8 gene knockdown by small hairpin RNA (shRNA). KLF8 expression in four NPC cell lines was examined by quantitative polymerase chain reaction (qPCR) and western blotting. KLF8 was knocked down in the SUNE1-5-8F/Sh-KLF8 cell line using shRNA, and the resulting stable cell line SUNE1-5-8F-sh-KLF8 was transplanted into nude mice in order to observe tumor formation and invasion...
June 2015: Oncology Letters
Xinpeng Shi, Xiaoyong Luo, Qingqing Yan, Wenjing Zhang, Yao Wu, Mengnan Zhang, Jinjun Zhao, Ying Peng, Ye Chen, Yali Zhang, Cunlong Chen, Tianming Cheng, Chudi Chen, Side Liu, Yang Bai, Jide Wang
KLF8 is a member of the KLF transcription factor family that plays an important role in oncogenesis. However, the role of KLF8 in colorectal cancer remains unknown. The aims of the present study were to examine KLF8 expression in colorectal cancers, to determine the role of KLF8 in cell differentiation and to investigate the antiproliferative effect of KLF8 silencing. The expression of KLF8 and phospho-ERK proteins was analyzed, and the effects of KLF8 suppression on cell differentiation and growth were evaluated...
September 2015: Oncology Reports
Marina Dobrivojević, Nikola Habek, Katarina Kapuralin, Marija Ćurlin, Srećko Gajović
Krüppel-like transcription factor 8 (KLF8) is a transcription factor suggested to be involved in various cellular events, including malignant cell transformation, still its expression in the adult rodent brain remained unknown. To analyze Klf8 in the mouse brain and to identify cell types expressing it, a specific transgenic Klf8(Gt1Gaj) mouse was used. The resulting Klf8 gene-driven β-galactosidase activity was visualized by X-gal histochemical staining of the brain sections. The obtained results were complemented by in situ RNA hybridization and immunohistochemistry...
October 1, 2015: Gene
Tianshu Li, Heng Lu, Debarati Mukherjee, Satadru K Lahiri, Chao Shen, Lin Yu, Jihe Zhao
Krüppel-like factor 8 (KLF8) is a dual transcriptional factor critical for breast cancer progression. Epidermal growth factor receptor (EGFR) is frequently overexpressed in aggressive such as triple-negative breast cancer and associated with poor clinical outcomes. Here we report a novel KLF8-EGFR signaling axis in breast cancer. We identified a highly correlated co-overexpression between KLF8 and EGFR in invasive breast cancer cells and patient tumor samples. Overexpression of KLF8 in the non-tumorigenic MCF-10A cells induced the expression of EGFR, whereas knockdown of KLF8 from the MDA-MB-231 cells decreased it...
August 28, 2015: Oncotarget
Sara A Hurvitz, Ondrej Kalous, Dylan Conklin, Amrita J Desai, Judy Dering, Lee Anderson, Neil A O'Brien, Teodora Kolarova, Richard S Finn, Ronald Linnartz, David Chen, Dennis J Slamon
Everolimus (RAD001, Afinitor(®)) is an oral, selective mTOR inhibitor recently approved by the US-FDA in combination with exemestane for treatment of hormone receptor positive advanced breast cancer. To date, no molecular predictors of response to everolimus in breast cancer have been identified. We hypothesized predictive markers could be identified using preclinical models. Using a molecularly characterized panel of human breast cancer and immortalized breast epithelial cell lines, we determined sensitivity to everolimus alone or in combination with ER- or HER2- targeted therapy...
February 2015: Breast Cancer Research and Treatment
Xiao-Jie Lu, Yan Shi, Jin-Lian Chen, Shijie Ma
Hepatocellular carcinoma (HCC) is a disease with a high incidence and mortality rate worldwide. However, the mechanisms underlying its pathogenesis are still elusive. In recent years, studies on functions of Krüppel-like factors (KLFs) in HCC have shed new light on this field. To date, five members (KLF4, KLF6, KLF8, KLF9, and KLF17) in the KLF family have been reported to function in the pathogenesis of HCC in multiple ways, which hold the potential of deepening and widening our understanding in the initiation and progression of HCC...
February 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Ming-Yuan Tsai, Yu-Fen Lu, Yu-Hsiu Liu, Huang-Wei Lien, Chang-Jen Huang, Jen-Leih Wu, Sheng-Ping L Hwang
Krüppel-like factor 8 (Klf8) is a zinc-finger transcription factor implicated in cell proliferation, and cancer cell survival and invasion; however, little is known about its role in normal embryonic development. Here, we show that Klf8 is required for normal cerebellar development in zebrafish embryos. Morpholino knockdown of klf8 resulted in abnormal cerebellar primordium morphology and the induction of p53 in the brain region at 24 hours post-fertilization (hpf). Both p53-dependent reduction of cell proliferation and augmentation of apoptosis were observed in the cerebellar anlage of 24 hpf-klf8 morphants...
September 2015: Developmental Neurobiology
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