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https://www.readbyqxmd.com/read/28410006/chaperone-mediated-autophagy-prevents-cellular-transformation-by-regulating-myc-proteasomal-degradation
#1
Luciana R Gomes, Carlos F M Menck, Ana Maria Cuervo
Chaperone-mediated autophagy (CMA), a selective form of protein lysosomal degradation, is maximally activated in stress situations to ensure maintenance of cellular homeostasis. CMA activity decreases with age and in several human chronic disorders, but in contrast, in most cancer cells, CMA is upregulated and required for tumor growth. However, the role of CMA in malignant transformation remains unknown. In this study, we demonstrate that CMA inhibition in fibroblasts augments the efficiency of MYC/c-Myc-driven cellular transformation...
March 2, 2017: Autophagy
https://www.readbyqxmd.com/read/28367986/protein-coding-genes-in-b-chromosomes-of-the-grasshopper-eyprepocnemis-plorans
#2
Beatriz Navarro-Domínguez, Francisco J Ruiz-Ruano, Josefa Cabrero, José María Corral, María Dolores López-León, Timothy F Sharbel, Juan Pedro M Camacho
For many years, parasitic B chromosomes have been considered genetically inert elements. Here we show the presence of ten protein-coding genes in the B chromosome of the grasshopper Eyprepocnemis plorans. Four of these genes (CIP2A, GTPB6, KIF20A, and MTG1) were complete in the B chromosome whereas the six remaining (CKAP2, CAP-G, HYI, MYCB2, SLIT and TOP2A) were truncated. Five of these genes (CIP2A, CKAP2, CAP-G, KIF20A, and MYCB2) were significantly up-regulated in B-carrying individuals, as expected if they were actively transcribed from the B chromosome...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#3
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28239848/protein-phosphatase-2a-regulation-of-markers-of-extracellular-matrix-remodelling-in-hepatocellular-carcinoma-cells-functional-consequences-for-tumour-invasion
#4
M P Ward, J P Spiers
BACKGROUND AND PURPOSE: A hallmark of tumour invasion is breakdown of the extracellular matrix due to dysregulation of the matrix metalloproteinase (MMP) system. While our understanding of how this is regulated by kinase signalling pathways is well established, its counter-regulation by protein phosphatases (PP) is poorly understood. Therefore, we investigated the effect of PP inhibition on markers of extracellular remodelling and how PP2A activity modulated MMP-9 abundance and function of Hep3B cells...
February 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28222497/correction-lapatinib-inhibits-cip2a-pp2a-p-akt-signaling-and-induces-apoptosis-in-triple-negative-breast-cancer-cells
#5
Chun-Yu Liu, Ming-Hung Hu, Chia-Jung Hsu, Chun-Teng Huang, Duen-Shian Wang, Wen-Chun Tsai, Yi-Ting Chen, Chia-Han Lee, Pei-Yi Chu, Chia-Chi Hsu, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
No abstract text is available yet for this article.
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174209/oncoprotein-cip2a-is-stabilized-via-interaction-with-tumor-suppressor-pp2a-b56
#6
Jiao Wang, Juha Okkeri, Karolina Pavic, Zhizhi Wang, Otto Kauko, Tuuli Halonen, Grzegorz Sarek, Päivi M Ojala, Zihe Rao, Wenqing Xu, Jukka Westermarck
Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast two-hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N-terminal CIP2A fragment (amino acids 1-560) at 3...
March 2017: EMBO Reports
https://www.readbyqxmd.com/read/28101248/expression-of-cancerous-inhibitor-of-protein-phosphatase-2a-in-human-triple-negative-breast-cancer-correlates-with-tumor-survival-invasion-and-autophagy
#7
Shan Li, Ting-Ting Feng, Yang Guo, Xianjun Yu, Qiuyue Huang, Liang Zhang, Wei Tang, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently characterized oncoprotein which is involved in the progression of several human malignancies. The present study aimed to investigate its biological function in human triple negative breast cancer (TNBC). The expression of CIP2A in TNBC cells was examined and it was observed that CIP2A was elevated in the TNBC cell line compared with poorly invasive breast cancer cells. CIP2A depletion in TNBC cell lines inhibited proliferation, and induced apoptosis and autophagy...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28068327/cip2a-confirms-its-prognostic-value-in-triple-negative-breast-cancer
#8
I Cristóbal, S Zazo, B Torrejón, M Pedregal, J Madoz-Gúrpide, A Lluch, P Eroles, A Rovira, J Albanell, J García-Foncillas, F Rojo
No abstract text is available yet for this article.
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28027514/egfr-independent-elk1-cip2a-signalling-mediates-apoptotic-effect-of-an-erlotinib-derivative-td52-in-triple-negative-breast-cancer-cells
#9
Chun-Yu Liu, Tzu-Ting Huang, Chun-Teng Huang, Ming-Hung Hu, Duen-Shian Wang, Wan-Lun Wang, Wen-Chun Tsai, Chia-Han Lee, Ka-Yi Lau, Hsiu-Ping Yang, Ming-Huang Chen, Chung-Wai Shiau, Ling-Ming Tseng, Kuen-Feng Chen
OBJECTIVES: Cancerous inhibitor of protein phosphatase 2A (CIP2A) has emerged as a therapeutic determinant mediating the anti-cancer effects of several new agents. We investigated the efficacy and mechanism of TD52, an erlotinib derivative with minimal p-EGFR inhibition but significant CIP2A downregulation, in triple-negative breast cancer (TNBC) cells. METHODS: TNBC lines were used for in vitro studies. Cell apoptosis was examined by flow cytometry and Western blot...
February 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/27779687/gambogenic-acid-induces-proteasomal-degradation-of-cip2a-and-sensitizes-hepatocellular-carcinoma-to-anticancer-agents
#10
Xian-Jun Yu, Qun Zhao, Xuan-Bin Wang, Jing-Xuan Zhang, Xiao-Bo Wang
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is overexpressed in many human malignancies. It regulates phosphorylated AKT and stabilizes c‑Myc in cell proliferation and tumor formation, suggesting that CIP2A plays an essential role in the development of cancer. In the present study, we report that a natural compound, gambogenic acid (GEA), induced the degradation of CIP2A via the ubiquitin‑proteasome pathway. Interestingly, the combination of GEA and proteasome inhibitors potentiated the accumulation of ubiquitinated CIP2A and aggresome formation...
December 2016: Oncology Reports
https://www.readbyqxmd.com/read/27694903/cip2a-promotes-cell-cycle-progression-in-triple-negative-breast-cancer-cells-by-regulating-the-expression-and-nuclear-export-of-p27kip1
#11
H Liu, H Qiu, Y Song, Y Liu, H Wang, M Lu, M Deng, Y Gu, J Yin, K Luo, Z Zhang, X Jia, G Zheng, Z He
Triple-negative breast cancer (TNBC) is very aggressive and currently has no specific therapeutic targets; as a consequence, TNBC exhibits poor clinical outcome. In this study, we showed that cancerous inhibitor of protein phosphatase 2A (Cip2a) represents a promising target in TNBC because Cip2a was highly expressed in TNBC cells and tumor tissues, and its expression showed an inverse correlation with overall survival in patients with TNBC. We found that inhibition of Cip2a in TNBC cells induced cell cycle arrest at the G2/M phase, inhibited cell proliferation and delayed tumor growth in the xenograft model...
April 6, 2017: Oncogene
https://www.readbyqxmd.com/read/27649840/cip2a-is-a-poor-prognostic-factor-and-can-be-a-diagnostic-marker-in-papillary-thyroid-carcinoma
#12
Ting-Ting Chao, Hung-Chune Maa, Cheng-Yi Wang, Dee Pei, Yao-Jen Liang, Yi-Feng Yang, Shuo-Jiun Chou, Yen-Lin Chen
Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma. CIP2A has recently been described as a prognostic marker in many cancers. In this study, we assessed the value of this novel prognostic marker in PTC. A total of 178 surgical specimens of both benign and malignant thyroid tumors were collected. Immunohistochemical staining for CIP2A, HBME-1, galectin-3, and CK19 was performed. Western blotting for CIP2A was also performed. CIP2A was expressed in 85.3% of malignant tumors and 12...
December 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/27574003/genistein-targets-the-cancerous-inhibitor-of-pp2a-to-induce-growth-inhibition-and-apoptosis-in-breast-cancer-cells
#13
Qingxia Zhao, Ming Zhao, Amanda B Parris, Ying Xing, Xiaohe Yang
Genistein is a soy isoflavone with phytoestrogen and tyrosine kinase inhibitory properties. High intake of soy/genistein has been associated with reduced breast cancer risk. Despite the advances in genistein-mediated antitumor studies, the underlying mechanisms remain unclear. In the present study, we investigated genistein-induced regulation of the cancerous inhibitor of protein phosphatase 2A (CIP2A), a novel oncogene frequently overexpressed in breast cancer, and its functional impact on genistein-induced growth inhibition and apoptosis...
September 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27556014/the-broken-off-switch-in-cancer-signaling-pp2a-as-a-regulator-of-tumorigenesis-drug-resistance-and-immune-surveillance
#14
REVIEW
Peter P Ruvolo
Aberrant activation of signal transduction pathways can transform a normal cell to a malignant one and can impart survival properties that render cancer cells resistant to therapy. A diverse set of cascades have been implicated in various cancers including those mediated by serine/threonine kinases such RAS, PI3K/AKT, and PKC. Signal transduction is a dynamic process involving both "On" and "Off" switches. Activating mutations of RAS or PI3K can be viewed as the switch being stuck in the "On" position resulting in continued signaling by a survival and/or proliferation pathway...
December 2016: BBA Clinical
https://www.readbyqxmd.com/read/27484817/cip2a-regulates-proliferation-and-apoptosis-of-multiple-myeloma-cells
#15
Zhuanzhen Zheng, Zhenhua Qiao, Wenliang Chen, Rong Gong, Yalin Wang, Lianrong Xu, Yanping Ma, Li Zhang, Yujin Lu, Bo Jiang, Guoxia Li, Chunxia Dong
Multiple myeloma (MM) is one of the most common causes of mortality from hematological malignancy in China. Recent studies have demonstrated that cancerous inhibitor of protein phosphatase 2A (CIP2A) may exhibit a role in promoting the growth of cancer; however, the function of CIP2A in MM remains unknown. In the present study, the expression and molecular mechanism underlying the effects of CIP2A in patients with MM and in MM cell lines were elucidated. Firstly, the expression of CIP2A was detected in patients with MM and in MM cell lines by reverse transcription‑quantitative polymerase chain reaction...
September 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27350399/cucurbitacin-b-reverses-multidrug-resistance-by-targeting-cip2a-to-reactivate-protein-phosphatase-2a-in-mcf-7-adriamycin-cells
#16
Fen Cai, Liang Zhang, Xiangling Xiao, Chao Duan, Qiuyue Huang, Chunsheng Fan, Jian Li, Xuewen Liu, Shan Li, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in various tumors. A previous study found that CIP2A expression is associated with doxorubicin (Dox) resistance. In the present study, we investigated whether cucurbitacin B (CuB), a natural anticancer compound found in Cucurbitaceae, reversed multidrug resistance (MDR) and downregulated CIP2A expression in MCF-7/Adriamycin (MCF-7/Adr) cells, a human breast multidrug-resistant cancer cell line. CuB treatment significantly suppressed MCF-7/Adr cell proliferation, and reversed Dox resistance...
August 2016: Oncology Reports
https://www.readbyqxmd.com/read/27348236/the-expression-of-cancerous-inhibitor-protein-phosphatase-2a-in-chronic-rhinosinusitis-with-nasal-polyps
#17
Emma Terna, Annika Luukkainen, Miia Seppälä, Risto Renkonen, Heini Huhtala, Satu Tommola, Timo Paavonen, Paula Kauppi, Olli Tynninen, Leila Jeskanen, Sanna Toppila-Salmi
CONCLUSION: The study suggests that cancerous inhibitor of protein phosphatase 2A (CIP2A) expression and eosinophilia associate with chronic rhinosinusitis with nasal polyps with aspirin exacerbated respiratory disease (CRSwNP + AERD). Further studies with a larger sample size are needed to evaluate further the role of CIP2A and related pathways in CRSwNP + AERD. OBJECTIVES: Low prostaglandin E2 levels putatively associate with CRSwNP + AERD and decreased c-Myc levels...
November 2016: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/27144172/cancerous-inhibitor-of-pp2a-silencing-inhibits-proliferation-and-promotes-apoptosis-in-human-multiple-myeloma-cells
#18
Xi Yang, Yaping Zhang, Hong Liu, Zenghua Lin
Multiple myeloma is the second most prevalent type of blood cancer, representing approximately 1% of all cancers and 2% of all cancer deaths. There is therefore a strong need to identify critical targets in multiple myeloma neoplasia and progression. Cancerous inhibitor of PP2A (CIP2A) is a human oncoprotein that regulates cancer cell viability and anchorage-independent growth and induces apoptosis. The present study investigated CIP2A function in the human multiple myeloma cell lines RPMI-8226 and NCI-H929 to determine whether it can serve as a potential therapeutic target...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27100879/cip2a-promotes-t-cell-activation-and-immune-response-to-listeria-monocytogenes-infection
#19
Christophe Côme, Anna Cvrljevic, Mohd Moin Khan, Irina Treise, Thure Adler, Juan Antonio Aguilar-Pimentel, Byron Au-Yeung, Eleonora Sittig, Teemu Daniel Laajala, Yiling Chen, Sebastian Oeder, Julia Calzada-Wack, Marion Horsch, Tero Aittokallio, Dirk H Busch, Markus W Ollert, Frauke Neff, Johannes Beckers, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Zhi Chen, Riitta Lahesmaa, Jukka Westermarck
The oncoprotein Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) is overexpressed in most malignancies and is an obvious candidate target protein for future cancer therapies. However, the physiological importance of CIP2A-mediated PP2A inhibition is largely unknown. As PP2A regulates immune responses, we investigated the role of CIP2A in normal immune system development and during immune response in vivo. We show that CIP2A-deficient mice (CIP2AHOZ) present a normal immune system development and function in unchallenged conditions...
2016: PloS One
https://www.readbyqxmd.com/read/27090640/cross-talk-between-wnt-%C3%AE-catenin-and-cip2a-plk1-signaling-in-prostate-cancer-promising-therapeutic-implications
#20
REVIEW
Ion Cristóbal, Federico Rojo, Juan Madoz-Gúrpide, Jesús García-Foncillas
Aberrant activation of the Wnt/β-catenin pathway and polo-like kinase 1 (Plk1) overexpression represent two common events in prostate cancer with relevant functional implications. This minireview analyzes their potential therapeutic significance in prostate cancer based on their role as androgen receptor (AR) signaling regulators and the pivotal role of the tumor suppressor protein phosphatase 2A (PP2A) modulating these pathways.
June 15, 2016: Molecular and Cellular Biology
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