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Dong-Dong Cheng, He-Chun Lin, Shi-Jie Li, Ming Yao, Qing-Cheng Yang, Cun-Yi Fan
To discover tumor-associated proteins in osteosarcoma, a quantitative proteomic analysis was performed to identify proteins that were differentially expressed between osteosarcoma and human osteoblastic cells. Through clinical screening and a functional evaluation, chromosome segregation 1-like (CSE1L) protein was found to be related to the growth of osteosarcoma cells. To date, little is known about the function and underlying mechanism of CSE1L in osteosarcoma. In the present study, we show that knockdown of CSE1L inhibits osteosarcoma growth in vitro and in vivo...
April 7, 2017: Scientific Reports
Kun Jiang, Kevin Neill, Daniel Cowden, Jason Klapman, Steven Eschrich, José Pimiento, Mokenge P Malafa, Domenico Coppola
BACKGROUND: Identifying the molecular switch responsible for the neoplastic progression of Barrett's esophagus (BE) and initiation of adenocarcinoma (ADC) is clinically essential and it will have a profound impact on patient diagnosis, prognosis, and treatment. The cellular apoptosis susceptibility gene CAS/CSE1L is overexpressed in various cancers, including a rare report on esophageal ADC; however, its expression in BE neoplasia has not been addressed. MATERIALS AND METHODS: We investigated the expression of the CAS/CSE1L protein immunohistochemically in 56 esophageal resection specimens for ADC arising in BE...
December 9, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Ming-Chung Jiang
CSE1L (chromosome segregation 1-like protein), also named as CAS (cellular apoptosis susceptibility protein), is highly expressed in most cancer types. CSE1L/CAS is a multiple functional protein that plays roles in apoptosis, cell survival, chromosome assembly, nucleocytoplasmic transport, microvesicle formation, and cancer metastasis; some of the functions are explicitly correlated. CSE1L is also a cancer serum biomarker. The phosphorylation of CAS is regulated by the extracellular signal-regulated kinase (ERK)...
October 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jose M Pimiento, Kevin G Neill, Evita Henderson-Jackson, Steven A Eschrich, Dung-Tsa Chen, Kazim Husain, David Shibata, Domenico Coppola, Mokenge P Malafa
Human cellular apoptosis susceptibility (chromosomal segregation 1-like, CSE1L) gene plays a role in nuclear-to-cytoplasm transport and chromosome segregation during mitosis, cellular proliferation, and apoptosis. CSE1L is involved in colon carcinogenesis. CSE1L gene expression was assessed with three data sets using Affymetrix U133 + gene chips on normal human colonic mucosa (NR), adenomas (ADs), and colorectal carcinoma (CRC). CSE1L protein expression in CRC, AD, and NR from the same patients was measured by immunohistochemistry using a tissue microarray...
October 2016: American Journal of Pathology
Beata Ostasiewicz, Paweł Ostasiewicz, Kamila Duś-Szachniewicz, Katarzyna Ostasiewicz, Piotr Ziółkowski
Biomarkers have been described as the future of oncology. Modern proteomics provide an invaluable tool for the near‑whole proteome screening for proteins expressed differently in neoplastic vs. healthy tissues. However, in order to select the most promising biomarkers, an independent method of validation is required. The aim of the current study was to propose a methodology for the validation of biomarkers. Due to material availability the majority of large scale biomarker studies are performed using formalin‑fixed paraffin‑embedded (FFPE) tissues, therefore these were selected for use in the current study...
June 2016: Molecular Medicine Reports
Srividya Vaidyanathan, Pulari U Thangavelu, Pascal H G Duijf
BACKGROUND: Ran GTPase regulates nuclear import, nuclear export, and mitotic spindle assembly. The multifunctional involvement of seventeen Ran GTPase components in these processes has complicated research into how each contributes to cancer development. OBJECTIVE: To assess whether individual and process-specific misexpression of Ran GTPase components contribute to chromosome instability (CIN) and worsen breast cancer patient prognosis. METHODS: Using publicly available datasets, we studied the degree of misexpression of all Ran GTPase signaling components in breast cancer, assessed their involvement in CIN and used four clinical tests to evaluate whether their misregulation may constitute independent prognostic predictors...
October 2016: Targeted Oncology
Woan-Ruoh Lee, Shing-Chuan Shen, Pei-Ru Wu, Chia-Lun Chou, Yi-Hsien Shih, Chung-Min Yeh, Kun-Tu Yeh, Ming-Chung Jiang
The Ras/ERK (extracellular signal-regulated protein kinase) and cAMP/PKA (protein kinase A) pathways are essential for the transcriptional activities of CREB (cAMP response element binding protein) and MITF (microphthalmia-associated transcription factor) in melanogenesis and the progression of melanoma. However, the interaction between Ras/ERK and cAMP/PKA pathways in the melanogenesis and progression of melanoma is not fully known. Here, we report that CSE1L (chromosome segregation 1-like protein) regulates cAMP/PKA-induced CREB and MITF expressions as well as Ras-induced ERK1/2 phosphorylation...
November 2016: Molecular Carcinogenesis
Ulvi M Yuksel, Ibrahim Turker, Gulay Dilek, Lutfi Dogan, Mehmet A Gulcelik, Berna Oksuzoglu
BACKGROUND: CSE1L (chromosome segregation 1-like) is the human homologue to the yeast gene CSE1, and is related to invasion and metastasis in cancer progression. The aim of this study was to investigate the potential role of CSE1L expression in distant metastasis of breast cancer. PATIENTS AND METHODS: A total of 71 breast cancer patients were included in this study. Clinical characteristics and CSE1L status were evaluated. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded archival breast tumor tissue...
2015: Oncology Research and Treatment
Satoshi Okimoto, Jiying Sun, Atsuhiko Fukuto, Yasunori Horikoshi, Shun Matsuda, Tomonari Matsuda, Masae Ikura, Tsuyoshi Ikura, Shinichi Machida, Hitoshi Kurumizaka, Yoichi Miyamoto, Masahiro Oka, Yoshihiro Yoneda, Yoshiaki Kiuchi, Satoshi Tashiro
Homologous recombinational repair (HR) is one of the major repair systems for DNA double-strand breaks. RAD51 is a key molecule in HR, and the RAD51 concentration in the cell nucleus increases after DNA damage induction. However, the mechanism that regulates the intracellular distribution of RAD51 is still unclear. Here, we show that hCAS/CSE1L associates with RAD51 in human cells. We found that hCAS/CSE1L negatively regulates the nuclear protein level of RAD51 under normal conditions. hCAS/CSE1L is also required to repress the DNA damage-induced focus formation of RAD51...
September 2015: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Woan-Ruoh Lee, Shing-Chuan Shen, Yi-Hsien Shih, Chia-Lun Chou, Jonathan Te-Peng Tseng, Szu-Ying Chin, Kao-Hui Liu, Yen-Chou Chen, Ming-Chung Jiang
BACKGROUND: Although targeted therapies have improved the clinical outcomes of cancer treatment, tumors resistance to targeted drug are often detected too late and cause mortality. CSE1L is secreted from tumor and its phosphorylation is regulated by ERK1/2. ERK1/2 is located downstream of various growth factor receptors and kinases, the targets of most targeted drugs. Serum phospho-CSE1L may be a marker for monitoring the efficacy of targeted therapy. METHODS: We used mice tumor xenograft model to study the assay of serum phosphorylated CSE1L for early detecting the efficacy of targeted drugs...
June 13, 2015: Journal of Translational Medicine
Szu-Ying Chin, Pei-Ru Wu, Yi-Hsien Shih, Chung-Min Yeh, Woan-Ruoh Lee, Shing-Chuan Shen, Kun-Tu Yeh, Ming-Chung Jiang, Jonathan Te-Peng Tseng
Melanoma is difficult to treat when it has metastasized. Discrimination between melanoma and benign nevi in melanocytic lesions is crucial for identifying melanomas and consequently improving melanoma treatment and prognosis. The chromosome segregation 1-like (CSE1L) protein has been implicated in cancer progression and is regulated by phosphorylation by extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, a critical pathway in melanoma progression. We studied phosphorylated CSE1L expression in human melanoma and benign nevi specimens...
2015: International Journal of Clinical and Experimental Pathology
Rong Xu, David W Greening, Alin Rai, Hong Ji, Richard J Simpson
Secretion and exchange of extracellular vesicles (EVs) by most cell types is emerging as a fundamental biological process. Although much is known about EVs, there is still a lack of definition as to how many naturally occurring EV subtypes there are and how their properties and functionalities might differ. This vexing issue is critical if EVs are to be fully harnessed for therapeutic applications. To address this question we have developed and describe here a sequential centrifugal ultrafiltration (SCUF) method to examine, in an unbiased manner, what EV subtypes are released in vitro into cell culture medium using the human colon carcinoma cell line LIM1863 as a model system...
October 1, 2015: Methods: a Companion to Methods in Enzymology
Ulvi Murat Yuksel, Gulay Dilek, Lutfi Dogan, Mehmet Ali Gulcelik, Ugur Berberoglu
AIM: CSE1L is the human homologue to the yeast gene CSE1 and CSE1L is a gene related to cancer progression. Thus, CSE1L may regulate the invasion and metastasis of breast cancer. The aim of this study is to show the relationship between CSE1L and axillary lymph node metastasis. METHODS: Sixty-six breast cancer patients were evaluated according to patient and tumor characteristics. Immunohistochemistry was carried out on formalin-fixed, paraffin-embedded archival breast tumor tissues...
March 2015: Tumori
Xiaohong Wang, Yiqiang Liu, Duanfang Shao, Ziliang Qian, Zhengwei Dong, Yun Sun, Xiaofang Xing, Xiaojing Cheng, Hong Du, Ying Hu, Yingai Li, Lin Li, Bin Dong, Ziyu Li, Aiwen Wu, Xiaojiang Wu, Zhaode Bu, Xianglong Zong, Guanshan Zhu, Qunsheng Ji, Xian-zi Wen, Lian-hai Zhang, Jia-fu Ji
BACKGROUND: Gastric cancer (GC) is an aggressive malignancy whose mechanisms of development and progression are poorly understood. The identification of prognosis-related genomic loci and genes may suffer from the relatively small case numbers and a lack of systematic validation in previous studies. METHODS: Array-based comparative genomic hybridization (aCGH) coupled with patient clinical information was applied to identify prognosis-related loci and genes with high-frequency recurrent gains in 129 GC patients...
January 2016: Gastric Cancer
Annalisa Lorenzato, Marta Biolatti, Giuseppe Delogu, Giampiero Capobianco, Cristiano Farace, Salvatore Dessole, Antonio Cossu, Francesco Tanda, Roberto Madeddu, Martina Olivero, Maria Flavia Di Renzo
The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells...
October 15, 2013: Experimental Cell Research
Ming-Chung Jiang, Chung-Min Yeh, Cheng-Jeng Tai, Hung-Chang Chen, Shu-Hui Lin, Tzu-Cheng Su, Shing-Chuan Shen, Woan-Ruoh Lee, Ching-Fong Liao, Li-Tzu Li, Ching-Hsiao Lee, Ying-Chun Chen, Kun-Tu Yeh, Chun-Chao Chang
BACKGROUND: Ras plays an important role in colorectal cancer progression. CSE1L (chromosome segregation 1-like) gene maps to 20q13, a chromosomal region that correlates with colorectal cancer development. We investigated the association of CSE1L with Ras in colorectal cancer progression. METHODS: The effect of CSE1L on metastasis-stimulating activity of Ras was studied in an animal model with tumor cells expressing CSE1L-specific shRNA and v-H-Ras. CSE1L expression was evaluated by the immunohistochemical analysis of 127 surgically resected colorectal tumors...
September 2013: American Journal of Surgery
Jin-Hui Zhu, De-Fei Hong, Yong-Mao Song, Li-Feng Sun, Zhi-Fei Wang, Jian-Wei Wang
The cellular apoptosis susceptibility (CSE1L) gene has been demonstrated to regulate multiple cellular mechanisms including the mitotic spindle check point as well as proliferation and apoptosis. However, the importance of CSE1L in human colon cancer is largely unknown. In the present study, we examined expression levels of CSE1L mRNA by semiquantitative RT-PCR. A lentivirus-mediated small interfering RNA (siRNA) was used to knock down CSE1L expression in the human colon cancer cell line RKO. Changes in CSE1L target gene expression were determined by RT-PCR...
2013: Asian Pacific Journal of Cancer Prevention: APJCP
Cheng-Jeng Tai, Tzu-Cheng Su, Ming-Chung Jiang, Hung-Chang Chen, Shing-Chuan Shen, Woan-Ruoh Lee, Ching-Fong Liao, Ying-Chun Chen, Shu-Hui Lin, Li-Tzu Li, Ko-Hung Shen, Chung-Min Yeh, Kun-Tu Yeh, Ching-Hsiao Lee, Hsin-Yi Shih, Chun-Chao Chang
BACKGROUND: Colorectal carcinomas spread easily to nearby tissues around the colon or rectum, and display strong potential for invasion and metastasis. CSE1L, the chromosome segregation 1-like protein, is implicated in cancer progression and is located in both the cytoplasm and nuclei of tumor cells. We investigated the prognostic significance of cytoplasmic vs. nuclear CSE1L expression in colorectal cancer. METHODS: The invasion- and metastasis-stimulating activities of CSE1L were studied by in vitro invasion and animal experiments...
2013: Journal of Translational Medicine
Kay Ka-Wai Li, Ling Yang, Jesse Chung-Sean Pang, Aden Ka-Yin Chan, Liangfu Zhou, Ying Mao, Yin Wang, Kin-Mang Lau, Wai Sang Poon, Zhifeng Shi, Ho-Keung Ng
MicroRNA-137 (miR-137) expression has been reported to be decreased in astrocytic tumors in two expression profiling studies but its role in the pathogenesis of oligodendroglial tumors is still limited. In this study, we demonstrate that miR-137 expression is significantly downregulated in a cohort of 35 oligodendroglial tumors and nine glioma cell lines compared with normal brains. Lower miR-137 expression is associated with shorter progressive-free survival and overall survival. Restoration of miR-137 expression in an oligodendroglial cells TC620, and also glioblastoma cells of U87 and U373 significantly suppressed cell growth, anchorage-independent growth, as well as invasion...
July 2013: Brain Pathology
Tobias Voigt, Claas Gerding-Reimers, Tuyen Thi Ngoc Tran, Sabrina Bergmann, Hugo Lachance, Beate Schölermann, Andreas Brockmeyer, Petra Janning, Slava Ziegler, Herbert Waldmann
A Prins cyclization between a polymer-bound aldehyde and a homoallylic alcohol served as the key step in the synthesis of tetrahydropyran derivatives. A phenotypic screen led to the identification of compounds that inhibit mitosis (as seen by the accumulation of round cells with condensed DNA and membrane blebs). These compounds were termed tubulexins as they target the CSE1L protein and the vinca alkaloid binding site of tubulin.
January 2, 2013: Angewandte Chemie
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