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https://www.readbyqxmd.com/read/27779687/gambogenic-acid-induces-proteasomal-degradation-of-cip2a-and-sensitizes-hepatocellular-carcinoma-to-anticancer-agents
#1
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...
October 20, 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
#2
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...
October 3, 2016: Oncogene
https://www.readbyqxmd.com/read/27649840/cip2a-is-a-poor-prognostic-factor-and-can-be-a-diagnostic-marker-in-papillary-thyroid-carcinoma
#3
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...
September 21, 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
#4
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
#5
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
#6
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
#7
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
#8
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...
June 27, 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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/27082429/oridonin-inhibits-gefitinib-resistant-lung-cancer-cells-by-suppressing-egfr-erk-mmp-12-and-cip2a-akt-signaling-pathways
#12
Xiangling Xiao, Zhongwei He, Wei Cao, Fen Cai, Liang Zhang, Qiuyue Huang, Chunsheng Fan, Chao Duan, Xiaobo Wang, Jiu Wang, Ying Liu
Oridonin (Ori), a diterpenoid compound extracted from traditional medicinal herbs, elicits antitumor effects on many cancer types. However, whether Ori can be used in gefitinib-resistant non-small cell lung cancer (NSCLC) cells remains unclear. This study investigated the antitumor activity and underlying mechanisms of Ori. Results demonstrated that this compound dose-dependently inhibited the proliferation, invasion, and migration of the gefitinib-resistant NSCLC cells in vitro. Ori also significantly downregulated the phosphorylation of EGFR, ERK, Akt, expression levels of matrix metalloproteinase-12 (MMP-12), and the cancerous inhibitor of protein phosphatase 2A (CIP2A)...
June 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27029072/hdac1-controls-cip2a-transcription-in-human-colorectal-cancer-cells
#13
Manjola Balliu, Cristina Cellai, Matteo Lulli, Anna Laurenzana, Eugenio Torre, Alessandro Maria Vannucchi, Francesco Paoletti
This work describes the effectiveness of HDAC-inhibitor (S)-2 towards colorectal cancer (CRC) HCT116 cells in vitro by inducing cell cycle arrest and apoptosis, and in vivo by contrasting tumour growth in mice xenografts. Among the multifaceted drug-induced events described herein, an interesting link has emerged between the oncoprotein histone deacetylase HDAC1 and the oncogenic Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) which is overexpressed in several cancers including CRCs. HDAC1 inhibition by (S)-2 or specific siRNAs downregulates CIP2A transcription in three different CRC cell lines, thus restoring the oncosuppressor phosphatase PP2A activity that is reduced in most cancers...
May 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/26987906/high-cip2a-levels-correlate-with-an-antiapoptotic-phenotype-that-can-be-overcome-by-targeting-bcl-xl-in-chronic-myeloid-leukemia
#14
C M Lucas, M Milani, M Butterworth, N Carmell, L J Scott, R E Clark, G M Cohen, S Varadarajan
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a predictive biomarker of disease progression in many malignancies, including imatinib-treated chronic myeloid leukemia (CML). Although high CIP2A levels correlate with disease progression in CML, the underlying molecular mechanisms remain elusive. In a screen of diagnostic chronic phase samples from patients with high and low CIP2A protein levels, high CIP2A levels correlate with an antiapoptotic phenotype, characterized by downregulation of proapoptotic BCL-2 family members, including BIM, PUMA and HRK, and upregulation of the antiapoptotic protein BCL-XL...
June 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/26985637/fty720-induced-enhancement-of-autophagy-protects-cells-from-fty720-cytotoxicity-in-colorectal-cancer
#15
Juan Li, Shu-Wei Wang, Dong-Sheng Zhang, Ye Sun, Chun-Yan Zhu, Qiang Fei, Jun Hu, Chuan Zhang, Yue-Ming Sun
FTY720, also known as fingolimod, is a widely used immunomodulator in multiple sclerosis and multiple organ transplantation. It is also an important protein phosphatase 2A (PP2A) activator. Based on this, a number of studies have recently demonstrated the cytotoxic effect of FTY720 in various cancers. Yet in colorectal cancer (CRC), the underlying mechanisms of FTY720 cytotoxicity remain less clear, especially the relationship between a drug and autophagy. We demonstrate here for the first time that FTY720 promotes the appearance of autophagic hallmarks such as autophagosome formation and light chain 3 (LC3)-II accumulation, indicating the participation of autophagy in FTY720 cytotoxicity on CRC...
May 2016: Oncology Reports
https://www.readbyqxmd.com/read/26962948/a-cytomegalovirus-peptide-specific-antibody-alters-natural-killer-cell-homeostasis-and-is-shared-in-several-autoimmune-diseases
#16
Yu Liu, Rong Mu, Ya-Ping Gao, Jie Dong, Lei Zhu, Yuyuan Ma, Yu-Hui Li, He-Qiu Zhang, Dong Han, Yu Zhang, Iain B McInnes, Jingang Zhang, Beifen Shen, Guang Yang, Zhan-Guo Li
Human cytomegalovirus (hCMV), a ubiquitous beta-herpesvirus, has been associated with several autoimmune diseases. However, the direct role of hCMV in inducing autoimmune disorders remains unclear. Here we report the identification of an autoantibody that recognizes a group of peptides with a conserved motif matching the Pp150 protein of hCMV (anti-Pp150) and is shared among patients with various autoimmune diseases. Anti-Pp150 also recognizes the single-pass membrane protein CIP2A and induces the death of CD56(bright) NK cells, a natural killer cell subset whose expansion is correlated with autoimmune disease...
March 9, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/26962939/cmv-and-nk-cells-an-unhealthy-tryst
#17
COMMENT
Cecilia Söderberg-Nauclér
Cytomegalovirus (CMV) has been associated with autoimmune diseases, but linking this common virus to disease pathology has been difficult. In this issue of Cell Host & Microbe, Liu et al. (2016) identify a CMV-cross-reactive autoantibody that also recognizes CIP2A on natural killer cells, possibly affecting their function in autoimmune patients.
March 9, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/26894380/cip2a-down-regulation-enhances-the-sensitivity-of-pancreatic-cancer-cells-to-gemcitabine
#18
Peng Xu, Jie Yao, Jin He, Long Zhao, Xiaodong Wang, Zhennan Li, Jianjun Qian
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein which participates in inhibiting tumor apoptosis in pancreatic cancer cells. Using immunohistochemical staining, we investigated the expression of CIP2A protein in 72 cases of human pancreatic ductal adenocarcinoma (PDAC) tissue and 27 cases of adjacent normal pancreatic tissue. The positive rate of CIP2A protein expression in pancreatic cancer tissue was70.83 %, which was significantly higher than that in adjacent non- cancerous pancreatic tissue (11...
March 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/26824320/lapatinib-inhibits-cip2a-pp2a-p-akt-signaling-and-induces-apoptosis-in-triple-negative-breast-cancer-cells
#19
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
We tested the efficacy of lapatinib, a dual tyrosine kinase inhibitor which interrupts the HER2 and epidermal growth factor receptor (EGFR) pathways, in a panel of triple-negative breast cancer (TNBC) cells, and examined the drug mechanism. Lapatinib showed an anti-proliferative effect in HCC 1937, MDA-MB-468, and MDA-MB-231 cell lines. Lapatinib induced significant apoptosis and inhibited CIP2A and p-Akt in a dose and time-dependent manner in the three TNBC cell lines. Overexpression of CIP2A reduced lapatinib-induced apoptosis in MDA-MB-468 cells...
February 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/26813457/clinical-significance-of-scip2a-levels-in-breast-cancer
#20
M-L Xing, Y-F Lu, D-F Wang, X-Y Zou, S-X Zhang, Z Yun
OBJECTIVE: It has previously found that human oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) was overexpressed in breast cancer, and was positively correlated with lymph node metastasis of the patients. This study aimed to investigate the association between serum CIP2A and prognosis of breast cancer. Then, we investigated whether CIP2A could be as a therapeutic target in breast cancer treatment. PATIENTS AND METHODS: Preoperative CIP2A levels of 240 patients with breast cancer and 480 cases of controls were measured by ELISA method...
2016: European Review for Medical and Pharmacological Sciences
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