Expression of CIP2A in renal cell carcinomas correlates with tumour invasion, metastasis and patients’ survival

Ren, Juchao; Li, W; Yan, Lei; Jiao, Wei; Tian, Sujian; Li, D; Tang, Yujie; Gu, Gang-Li; Liu, H; Xu, Zhonghua

doi:10.1038/bjc.2011.492

Cited by 55 publications

(52 citation statements)

References 36 publications

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“…When PP2A is inhibited by CIP2A, PP2A-mediated dephosphorylation of these oncoproteins is blocked, thus promoting anchorage-independent cell growth and in vivo tumor formation. CIP2A functions as an oncoprotein that promotes proliferation and aggressiveness of several cancer types including head and neck squamous cell carcinoma, oral squamous cell carcinoma, esophageal squamous cell carcinoma, colon, gastric, breast, prostate, tongue, lung, and cervical cancer, as well as acute myeloid leukemia (6,(9)(10)(11)(12). In addition, aberrant expression, mutations, and somatic alterations of the PP2A scaffold and regulatory subunits are frequently found in human breast, lung, colon, and skin cancers (13).…”

Section: Introductionmentioning

confidence: 99%

Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A

et al. 2017

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Abstract.We have shown that a novel STAT3 inhibitor arctigenin (Atn) induces significant cytotoxicity in triple-negative breast cancer (TNBC) cells. This study further delineated molecular mechanisms where by Atn triggered cytotoxicity in TNBC cells. We found Atn can also inhibit metastasis in TNBC cells through cancerous inhibitor of protein phosphatase 2A (CIP2A) pathway. CIP2A is an endogenous inhibitor of protein phosphatase 2A (PP2A), which can increase the migration and invasion of various cancer cells. PP2A is a tumor suppressor, which is functionally defective in various cancers. Atn-induced metastasis inhibition was associated with reactivation of PP2A, downregulation of CIP2A and Akt phosphorylation. Silencing CIP2A enhanced Atn-induced metastasis inhibition and apoptosis in TNBCs. Furthermore, ectopic expression of CIP2A or inhibition of PP2A in TNBC cells abolished the effects of Atn. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A, at least in part, promotes the anti-metastasis effect induced by Atn. Our findings disclose the novel therapeutic mechanism of this targeted agent, and suggest the therapeutic potential and feasibility of developing PP2A enhancers as a novel anticancer strategy.

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Section: Introductionmentioning

confidence: 99%

Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A

et al. 2017

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“…(14) This work investigated the correlation of the UHRF1 DNA level in plasma with clinical characteristics of breast cancer and its clinical significance in breast cancer diagnosis.…”

mentioning

confidence: 99%

Diagnostic and prognostic value of plasma and tissue ubiquitin‐like, containing PHD and RING finger domains 1 in breast cancer patients

Geng

Gao

et al. 2012

Cancer Science

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Ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1) has been reported to play an important role in breast carcinogenesis. This work investigated the correlation of UHRF1 DNA level in plasma with clinical characteristics of breast cancer and its clinical significance in breast cancer diagnosis. The expression of UHRF1 in primary breast cancer tissue was examined by Western blot. The UHRF1 DNA levels in plasma and UHRF1 mRNA expression in tissues were determined by accurate real-time quantitative PCR. The associations of UHRF1 levels with clinical variables were evaluated using standard statistical methods. The UHRF1 DNA in plasma of 229 breast cancer patients showed higher expression than healthy controls, which showed high specificity up to 76.2% at a sensitivity of 79.2%, and was significantly associated with c-erbB2 positive status, cancer stage and lymph node metastasis. High UHRF1 DNA level in plasma was significantly associated with short progression-free survival. The UHRF1 DNA level in plasma is highly correlative with breast cancer and its status and stage, and may be a potential independent diagnostic and prognostic factor for both breast cancer and the survival of breast cancer patients. (Cancer Sci 2013; 104: 194-199) B reast cancer is the most common malignant disease in women. Its prevalence rate has exhibited a clear increase in China. Furthermore, the mortality rate of breast cancer has risen by 38.9% in the past 20 years.(1) Current prognostic criteria only poorly predict the metastasis risk for an individual breast cancer patient due to a lack of specific biomarkers.(2) Thus, new prognostic biomarkers are urgently needed to identify breast cancer patients and those at the highest risk for developing metastasis.Gene-expression signatures of human primary breast cancers have shown more accurate prediction than current prognostic criteria.(3,4) ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1) is a newly discovered gene reported to have a function in maintaining DNA methylation by helping recruit DNA methyltransferase 1 (DNMT1) to hemimethylated DNA. Kim et al.(5) demonstrated its new role as a transcriptional corepressor in recruitment of histone methyltransferase G9a and other chromatin modifying enzymes to target promoters, and pointed out its dynamic regulation mode in cancer cells. The functional research of UHRF1 have made it a novel diagnostic marker in lung and bladder cancer.(6,7) Ubiquitinlike, containing PHD and RING finger domains 1-induced epigenetic changes, involving DNA methylation, histone modification, chromatin remodeling and recruitment of transcriptional complex on the breast cancer susceptibility gene 1 (BRCA1) promoter, are responsible for BRCA1 silencing in sporadic breast cancer.(8) These findings indicate that UHRF1 might play an important role in cancer development.Cancer patients generally exhibit an increasing amount of circulating DNA that comes from cancer tissues. (9)(10)(11) However, it is difficult to establish a unitary method for de...

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“…More recently, CIP2A expression has been found to be associated with the invasive function of fibroblast-like synoviocytes and synovial hyperplasia in rheumatoid arthritis (19). In addition, it has been reported that CIP2A immunostaining level positively correlated with metastasis in renal cell carcinomas (6). More recently, In addition, Zhai et al (20) found that CIP2A was overexpressed in osteosarcoma tissues, and that CIP2A depletion attenuated cell proliferation and invasion.…”

Section: A B C Discussionmentioning

confidence: 98%

“…CIP2A is a widespread oncogenic factor in human neoplasms (4)(5)(6)(7)(8)(9)3). Similar to the Ras oncogene, CIP2A is required for anchorage-independent cell growth and malignant transformation of human cells (4).…”

Section: A B C Discussionmentioning

confidence: 99%

“…Previous studies have shown that CIP2A serves a critical role in the progression of several cancer types, including head and neck squamous cell carcinoma, oral squamous cell carcinoma, oesophageal squamous cell carcinoma, colon, gastric, breast, prostate, tongue, lung, cervical cancer and acute myeloid leukaemia (3)(4)(5)(6)(7)(8)(9). In 2009, Côme et al (10) demonstrated that CIP2A is associated with clinical aggressivity in human breast cancer and promotes the malignant growth of breast cancer cells (10).…”

Section: Introductionmentioning

confidence: 99%

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Expression of cancerous inhibitor of protein phosphatase 2A in human triple negative breast cancer correlates with tumor survival, invasion and autophagy

Feng

Guo

et al. 2016

Oncology Letters

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Abstract. 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. In addition, CIP2A depletion inhibited invasion and migration of TNBC cells. Furthermore, CIP2A depletion downregulated Akt/mTOR/P70S6K phosphorylation. These results validate the role of CIP2A as a invasion-associated oncoprotein and established CIP2A as a promising therapeutic target of TNBC.

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Expression of CIP2A in renal cell carcinomas correlates with tumour invasion, metastasis and patients’ survival

Cited by 55 publications

References 36 publications

Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A

Arctigenin inhibits triple-negative breast cancers by targeting CIP2A to reactivate protein phosphatase 2A

Diagnostic and prognostic value of plasma and tissue ubiquitin‐like, containing PHD and RING finger domains 1 in breast cancer patients

Expression of cancerous inhibitor of protein phosphatase 2A in human triple negative breast cancer correlates with tumor survival, invasion and autophagy

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