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It summarizes carcinogenic roles of TNF-α and IL-1 and details cancer-specific functions across multiple tumor types, concluding that restoring PP2A activity supports effective anticancer 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compounds.",{"name":70,"@type":61,"acceptedAnswer":71},"How does the review connect PP2A activation to anticancer therapy?",{"text":72,"@type":64},"The conclusion emphasizes that activation of PP2A activity leads to effective anticancer therapy, based on the concept that PP2A inhibition drives progression.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},377037,1790802505,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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\n[https://doi.org/10.1007/s00432-023-04800-4](https://doi.org/10.1007/s00432-023-04800-4)  \nCancer progression by the okadaic acid class of tumor promotersand endogenous protein inhibitors of PP2A, SET and CIP2A  \nHirota Fujiki1 · Eisaburo Sueoka1 · Tatsuro Watanabe2 · Atsumasa Komori3 · Masami Suganuma4  \nReceived: 4 March 2023 / Accepted: 15 April 2023 / Published online: 25 April 2023 © The Author(s) 2023  \nAbstract  \nPurpose Okadaic acid class of tumor promoters are transformed into endogenous protein inhibitors of PP2A, SET, and CIP2A in human cancers. This indicates that inhibition of PP2A activity is a common mechanism of cancer progression in humans. It is important to study the roles of SET and CIP2A vis-à-vis their clinical significance on the basis of new information gathered from a search of PubMed.  \nResults and discussion The first part of this review introduces the carcinogenic roles of TNF-α and IL-1, which are induced by the okadaic acid class of compounds. The second part describes unique features of SET and CIP2A in cancer progression for several types of human cancer: (1) SET-expressing circulating tumor cells (SET-CTCs) in breast cancer,(2) knockdown of CIP2A and increased PP2A activity in chronic myeloid leukemia,(3) CIP2A and epidermal growth factor receptor (EGFR) activity in erlotinib sensitive-and resistant-non-small cell lung cancer,(4) SET antagonist EMQA plus radiation therapy against hepatocellular carcinoma,(5) PP2A inactivation as a common event in colorectal cancer,(6) prostate cancer susceptibility variants, homeobox transcription factor (HOXB13 T) and CIP2A T, and (7) SET inhibitor OP449 for pre-clinical investigation of pancreatic cancer. In the Discussion, the binding complex of SET is briefly introduced, and overexpression of SET and CIP2A proteins is discussed in relation to age-associated chronic inflammation (inflammaging) .  \nConclusion This review establishes the concept that inhibition of PP2A activity is a common mechanism of human cancer progression and activation of PP2A activity leads to effective anticancer therapy.  \nKeywords Cancer progression · CIP2A · Okadaic acid · PP2A · SET · TNF-α  \nIntroduction  \nOkadaic acid is a polyether compound of a C38 fatty acid, which is isolated from the black sponge, Halichondria okadai (Tachibana et al. 1981) . Okadaic acid acts as a tumor promoter in mouse skin initiated with 7,12-dimethylbenz(a) anthracene (DMBA) and is as potent as 12-O-tetradecanoylphorbol-13-acetate (TPA) (Table 1 , Fig. 1) (Suganuma et al. 1988 ; Hecker et al. 1967) . Because okadaic acid is a chemical inhibitor of serine /threonine protein phosphatase 1 and 2A (PP1 and PP2A) (Bialojan and Takai 1988), the mechanism of okadaic acid is different from activation of protein kinase C by TPA (Castagna et al. 1982) . Utilizing an assay based upon inhibition of [3H]okadaic acid binding to the particulate fraction of mouse skin, we identified  \n* Hirota Fujiki [uv4h-fjk@asahi-net.or.jp](uv4h-fjk@asahi-net.or.jp)  \nExtended author information available on the last page of the article  \nother compounds of the okadaic acid class as follows (Fujiki and Suganuma 1993): dinophysistoxin-1 (35-methylokadaic acid), isolated from the mussel Mytidus edulis (Murata et al. 1982); calyculin A, isolated from a marine sponge Discodermia calyx (Kato et al. 1986); and microcystin-LR and nodularin, isolated from toxic blue-green algae Cyanobacteria (Harada et al. 1988) (Fig. 1) . Moreover, okadaic acid is a more effective inhibitor of PP2A (50% inhibitory concentration, IC50 = 0.07 nM) than PP1 (IC50 = 3.4 nM), and other compounds of the okadaic acid class are equally effective against the purified catalytic subunits of PP1 and PP2A (IC50s = 0.1 to 0.7 nM) (Suganuma et al. 1992a) . Later, the compounds were additionally found to inhibit PP4 (IC50 = 0.1 to 0.4 nM) and PP5 (IC50 = 1.0 to 10 nM), which also belong to the class of","cbCaitoP7XfPGupT","https://ap.wps.com/l/cbCaitoP7XfPGupT","pdf",922488,"English","# Abstract\n## Purpose\n## Results and discussion\n## Conclusion\n# Introduction\n## Okadaic acid as a tumor promoter\n## Tumor-promoting activity of the okadaic acid class","[{\"question\":\"What mechanism links the okadaic acid class of tumor promoters to cancer progression?\",\"answer\":\"The review states that the okadaic acid class is transformed into endogenous protein inhibitors of PP2A, SET, and CIP2A, and that PP2A inhibition is a common mechanism of human cancer progression.\"},{\"question\":\"Which signaling and inflammatory factors are discussed in relation to the okadaic acid class compounds?\",\"answer\":\"The first part of the review introduces carcinogenic roles of TNF-α and IL-1, which are induced by the okadaic acid class of compounds.\"},{\"question\":\"How does the review connect PP2A activation to anticancer therapy?\",\"answer\":\"The conclusion emphasizes that activation of PP2A activity leads to effective anticancer therapy, based on the concept that PP2A inhibition drives progression.\"}]","Cancer progression by the okadaic acid class of tumor promoters and endogenous protein inhibitors of PP2A, SET and CIP2A | PDF",1790222816,23]