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Article ; Online: Cancer progression by the okadaic acid class of tumor promoters and endogenous protein inhibitors of PP2A, SET and CIP2A.

Fujiki, Hirota / Sueoka, Eisaburo / Watanabe, Tatsuro / Komori, Atsumasa / Suganuma, Masami

Journal of cancer research and clinical oncology

2023 Volume 149, Issue 11, Page(s) 9425–9433

Abstract: Purpose: 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 ... ...

Abstract	Purpose: 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. Results 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). Conclusion: 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.
MeSH term(s)	Male ; Humans ; Okadaic Acid ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinogens ; Lung Neoplasms/drug therapy ; Membrane Proteins/metabolism ; Cell Line, Tumor ; Intracellular Signaling Peptides and Proteins/genetics ; Liver Neoplasms ; Autoantigens/metabolism
Chemical Substances	Okadaic Acid (1W21G5Q4N2) ; Carcinogens ; Membrane Proteins ; Intracellular Signaling Peptides and Proteins ; Autoantigens
Language	English
Publishing date	2023-04-25
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-023-04800-4
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Book: Cellular interactions by environmental tumor promoters

Fujiki, Hirota

Tokyo, 1983

(Proceedings of the ... International Symposium of the Princess Takamatsu Cancer Research Fund ; 14)

1984

Author's details	ed. by Hirota Fujiki
Series title	Proceedings of the ... International Symposium of the Princess Takamatsu Cancer Research Fund ; 14
Collection
Keywords	Carcinogens / congresses ; Cell transformation, neoplastic / congresses
Size	XVI,402 S. : graph. Darst.
Publisher	Japan Scientific Societies Pr. u.a.
Publishing place	Tokyo u.a.
Publishing country	Japan
Document type	Book
HBZ-ID	HT002105524
ISBN	90-6764-038-7 ; 978-90-6764-038-1
Database	Catalogue ZB MED Medicine, Health

In stock of ZB MED Cologne/Königswinter

Shelf mark	Loan status	Location
1985 A 1835	order for loan	Magazin

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Article ; Online: Gist of Dr. Katsusaburo Yamagiwa's papers entitled "Experimental study on the pathogenesis of epithelial tumors" (I to VI reports).

Fujiki, Hirota

Cancer science

2014 Volume 105, Issue 2, Page(s) 143–149

Abstract: The concept of cancer and inflammation has a long history. Virchow's irritation theory based on human cancer engendered the essential role of inflammation in carcinogenesis. Drs. Yamagiwa and Ichikawa first published a comprehensive paper entitled " ... ...

Abstract	The concept of cancer and inflammation has a long history. Virchow's irritation theory based on human cancer engendered the essential role of inflammation in carcinogenesis. Drs. Yamagiwa and Ichikawa first published a comprehensive paper entitled "Experimental study on the pathogenesis of epithelial tumors" (I report) in 1915 in German, and went on to publish five more reports (1915-1924) under the same title. They succeeded in demonstrating that inflammation is an important carcinogenic factor, and the mechanisms are now being investigated by numerous scientists all over the world. In order to introduce Yamagiwa's work to modern cancer researchers, the essentials of their six reports have been translated into English as a short review. Scientists' comments on Yamagiwa's contribution are attached by way of introduction.
MeSH term(s)	Animals ; Carcinogenesis/pathology ; Epithelial Cells/pathology ; Humans ; Inflammation/pathology ; Neoplasms/etiology ; Neoplasms/pathology
Language	English
Publishing date	2014-01-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2115647-5
ISSN	1349-7006 ; 1349-7006
ISSN (online)	1349-7006
ISSN	1349-7006
DOI	10.1111/cas.12333
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Article ; Online: Structural and thermodynamic insights into antibody light chain tetramer formation through 3D domain swapping.

Sakai, Takahiro / Mashima, Tsuyoshi / Kobayashi, Naoya / Ogata, Hideaki / Duan, Lian / Fujiki, Ryo / Hengphasatporn, Kowit / Uda, Taizo / Shigeta, Yasuteru / Hifumi, Emi / Hirota, Shun

Nature communications

2023 Volume 14, Issue 1, Page(s) 7807

Abstract: Overexpression of antibody light chains in small plasma cell clones can lead to misfolding and aggregation. On the other hand, the formation of amyloid fibrils from antibody light chains is related to amyloidosis. Although aggregation of antibody light ... ...

Abstract	Overexpression of antibody light chains in small plasma cell clones can lead to misfolding and aggregation. On the other hand, the formation of amyloid fibrils from antibody light chains is related to amyloidosis. Although aggregation of antibody light chain is an important issue, atomic-level structural examinations of antibody light chain aggregates are sparse. In this study, we present an antibody light chain that maintains an equilibrium between its monomeric and tetrameric states. According to data from X-ray crystallography, thermodynamic and kinetic measurements, as well as theoretical studies, this antibody light chain engages in 3D domain swapping within its variable region. Here, a pair of domain-swapped dimers creates a tetramer through hydrophobic interactions, facilitating the revelation of the domain-swapped structure. The negative cotton effect linked to the β-sheet structure, observed around 215 nm in the circular dichroism (CD) spectrum of the tetrameric variable region, is more pronounced than that of the monomer. This suggests that the monomer contains less β-sheet structures and exhibits greater flexibility than the tetramer in solution. These findings not only clarify the domain-swapped structure of the antibody light chain but also contribute to controlling antibody quality and advancing the development of future molecular recognition agents and drugs.
MeSH term(s)	Humans ; Immunoglobulin Light Chains ; Amyloid/chemistry ; Crystallography, X-Ray ; Amyloidosis ; Thermodynamics
Chemical Substances	Immunoglobulin Light Chains ; Amyloid
Language	English
Publishing date	2023-12-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43443-4
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Article ; Online: Role of TNF-α-Inducing Protein Secreted by

Suganuma, Masami / Watanabe, Tatsuro / Sueoka, Eisaburo / Lim, In Kyoung / Fujiki, Hirota

Toxins

2021 Volume 13, Issue 3

Abstract: The tumor necrosis factor-α (TNF-α)-inducing ... ...

Abstract	The tumor necrosis factor-α (TNF-α)-inducing protein
MeSH term(s)	Animals ; Antigens, Bacterial/genetics ; Antigens, Bacterial/metabolism ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Outer Membrane Proteins/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Epithelial-Mesenchymal Transition ; Helicobacter Infections/complications ; Helicobacter Infections/diagnosis ; Helicobacter Infections/microbiology ; Helicobacter Infections/therapy ; Helicobacter pylori/genetics ; Helicobacter pylori/metabolism ; Helicobacter pylori/pathogenicity ; Host-Pathogen Interactions ; Humans ; Immediate-Early Proteins/metabolism ; Phosphoproteins/metabolism ; RNA-Binding Proteins/metabolism ; Risk Factors ; Stomach Neoplasms/metabolism ; Stomach Neoplasms/microbiology ; Stomach Neoplasms/pathology ; Stomach Neoplasms/prevention & control ; Tumor Necrosis Factor-alpha/metabolism ; Tumor Suppressor Proteins/metabolism ; Nucleolin
Chemical Substances	Antigens, Bacterial ; Bacterial Outer Membrane Proteins ; Bacterial Proteins ; HP-MP1 protein, Helicobacter pylori ; Immediate-Early Proteins ; Phosphoproteins ; RNA-Binding Proteins ; TNF protein, human ; Tipalpha protein, Helicobacter pylori ; Tumor Necrosis Factor-alpha ; Tumor Suppressor Proteins ; BTG2 protein, human (141490-22-4)
Language	English
Publishing date	2021-03-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins13030181
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Article ; Online: Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies

Masami Suganuma / Tatsuro Watanabe / Eisaburo Sueoka / In Kyoung Lim / Hirota Fujiki

Toxins, Vol 13, Iss 3, p

2021 Volume 181

Abstract: The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα , has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori ... ...

Abstract	The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα , has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 ( BTG2 /TIS21 ), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.
Keywords	EMT ; gastric cancer ; nucleolin ; HP-MP1 ; Tipα ; TNF-α ; Medicine ; R
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The concept of the okadaic acid class of tumor promoters is revived in endogenous protein inhibitors of protein phosphatase 2A, SET and CIP2A, in human cancers.

Fujiki, Hirota / Sueoka, Eisaburo / Watanabe, Tatsuro / Suganuma, Masami

Journal of cancer research and clinical oncology

2018 Volume 144, Issue 12, Page(s) 2339–2349

Abstract: Purpose: The okadaic acid class of tumor promoters, which are inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A), induced tumor promotion in mouse skin, rat glandular stomach, and rat liver. Endogenous protein inhibitors of PP2A, SET and CIP2A, ... ...

Abstract	Purpose: The okadaic acid class of tumor promoters, which are inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A), induced tumor promotion in mouse skin, rat glandular stomach, and rat liver. Endogenous protein inhibitors of PP2A, SET and CIP2A, were up-regulated in various human cancers, so it is vital to review the essential mechanisms of tumor promotion by the okadaic acid class compounds, together with cancer progression by SET and CIP2A in humans. Results and discussion: The first part of this review introduces the okadaic acid class compounds and the mechanism of tumor promotion: (1) inhibition of PP1 and PP2A activities of the okadaic acid class compounds; (2) some topics of tumor promotion; (3) TNF-α gene expression as a central mediator in tumor promotion; (4) exposure to the okadaic acid class of tumor promoters in relation to human cancer. The second part emphasizes the overexpression of SET and CIP2A in cancer progression, and the anticancer activity of SET antagonists as follows: (5) isolation and characterization of SET; (6) isolation and characterization of CIP2A; (7) progression of leukemia with SET; (8) progression of breast cancer with SET and CIP2A; (9) progression of lung cancer with SET; (10) anti-carcinogenic effects of SET antagonists OP449 and FTY720; and also (11) TNF-α-inducing protein of Helicobacter pylori, which is a clinical example of the okadaic acid pathway. Conclusions: The overexpression of endogenous protein inhibitors of PP2A, SET and CIP2A, is tightly linked to the progression of various human cancers, as well as Alzheimer's disease.
MeSH term(s)	Animals ; Autoantigens/genetics ; Autoantigens/metabolism ; Biomarkers, Tumor ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; DNA-Binding Proteins ; Disease Progression ; Environmental Exposure/adverse effects ; Enzyme Inhibitors/adverse effects ; Enzyme Inhibitors/chemistry ; Gene Expression Regulation, Neoplastic ; Helicobacter Infections/complications ; Helicobacter Infections/microbiology ; Helicobacter pylori/metabolism ; Histone Chaperones/antagonists & inhibitors ; Histone Chaperones/genetics ; Histone Chaperones/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins/antagonists & inhibitors ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Okadaic Acid/adverse effects ; Okadaic Acid/chemistry ; Protein Phosphatase 2/antagonists & inhibitors ; Protein Phosphatase 2/genetics ; Protein Phosphatase 2/metabolism ; Signal Transduction ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Autoantigens ; Biomarkers, Tumor ; CIP2A protein, human ; DNA-Binding Proteins ; Enzyme Inhibitors ; Histone Chaperones ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; SET protein, human ; Transcription Factors ; Tumor Necrosis Factor-alpha ; Okadaic Acid (1W21G5Q4N2) ; Protein Phosphatase 2 (EC 3.1.3.16)
Language	English
Publishing date	2018-10-20
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-018-2765-7
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Article ; Online: Structural and thermodynamic insights into antibody light chain tetramer formation through 3D domain swapping

Takahiro Sakai / Tsuyoshi Mashima / Naoya Kobayashi / Hideaki Ogata / Lian Duan / Ryo Fujiki / Kowit Hengphasatporn / Taizo Uda / Yasuteru Shigeta / Emi Hifumi / Shun Hirota

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 12

Abstract: Abstract Overexpression of antibody light chains in small plasma cell clones can lead to misfolding and aggregation. On the other hand, the formation of amyloid fibrils from antibody light chains is related to amyloidosis. Although aggregation of ... ...

Abstract	Abstract Overexpression of antibody light chains in small plasma cell clones can lead to misfolding and aggregation. On the other hand, the formation of amyloid fibrils from antibody light chains is related to amyloidosis. Although aggregation of antibody light chain is an important issue, atomic-level structural examinations of antibody light chain aggregates are sparse. In this study, we present an antibody light chain that maintains an equilibrium between its monomeric and tetrameric states. According to data from X-ray crystallography, thermodynamic and kinetic measurements, as well as theoretical studies, this antibody light chain engages in 3D domain swapping within its variable region. Here, a pair of domain-swapped dimers creates a tetramer through hydrophobic interactions, facilitating the revelation of the domain-swapped structure. The negative cotton effect linked to the β-sheet structure, observed around 215 nm in the circular dichroism (CD) spectrum of the tetrameric variable region, is more pronounced than that of the monomer. This suggests that the monomer contains less β-sheet structures and exhibits greater flexibility than the tetramer in solution. These findings not only clarify the domain-swapped structure of the antibody light chain but also contribute to controlling antibody quality and advancing the development of future molecular recognition agents and drugs.
Keywords	Science ; Q
Subject code	572
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human cancer stem cells are a target for cancer prevention using (-)-epigallocatechin gallate.

Fujiki, Hirota / Sueoka, Eisaburo / Rawangkan, Anchalee / Suganuma, Masami

Journal of cancer research and clinical oncology

2017 Volume 143, Issue 12, Page(s) 2401–2412

Abstract: Purpose: Our previous experiments show that the main constituent of green-tea catechins, (-)-epigallocatechin gallate (EGCG), completely prevents tumor promotion on mouse skin initiated with 7,12-dimethylbenz(a)anthracene followed by okadaic acid and ... ...

Abstract	Purpose: Our previous experiments show that the main constituent of green-tea catechins, (-)-epigallocatechin gallate (EGCG), completely prevents tumor promotion on mouse skin initiated with 7,12-dimethylbenz(a)anthracene followed by okadaic acid and that EGCG and green tea extract prevent cancer development in a wide range of target organs in rodents. Therefore, we focused our attention on human cancer stem cells (CSCs) as targets of cancer prevention and treatment with EGCG. Methods: The numerous reports concerning anticancer activity of EGCG against human CSCs enriched from cancer cell lines were gathered from a search of PubMed, and we hope our review of the literatures will provide a broad selection for the effects of EGCG on various human CSCs. Results: Based on our theoretical study, we discuss the findings as follows: (1) Compared with the parental cells, human CSCs express increased levels of the stemness markers Nanog, Oct4, Sox2, CD44, CD133, as well as the EMT markers, Twist, Snail, vimentin, and also aldehyde dehydrogenase. They showed decreased levels of E-cadherin and cyclin D1. (2) EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs. (3) EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs. (4) The inhibition of EGCG of the stemness of CSCs was weaker compared with parental cells. (5) The weak inhibitory activity of EGCG increased synergistically in combination with anticancer drugs. Conclusions: Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.
Language	English
Publishing date	2017-12
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-017-2515-2
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Article ; Online: Cancer Prevention with Green Tea and Its Principal Constituent, EGCG: from Early Investigations to Current Focus on Human Cancer Stem Cells.

Fujiki, Hirota / Watanabe, Tatsuro / Sueoka, Eisaburo / Rawangkan, Anchalee / Suganuma, Masami

Molecules and cells

2018 Volume 41, Issue 2, Page(s) 73–82

Abstract: Cancer preventive activities of green tea and its main constituent, (-)-epigallocatechin gallate (EGCG) have been extensively studied by scientists all over the world. Since 1983, we have studied the cancer chemopreventive effects of EGCG as well as ... ...

Abstract	Cancer preventive activities of green tea and its main constituent, (-)-epigallocatechin gallate (EGCG) have been extensively studied by scientists all over the world. Since 1983, we have studied the cancer chemopreventive effects of EGCG as well as green tea extract and underlying molecular mechanisms. The first part of this review summarizes ground-breaking topics with EGCG and green tea extract: 1) Delayed cancer onset as revealed by a 10-year prospective cohort study, 2) Prevention of colorectal adenoma recurrence by a double-blind randomized clinical phase II trial, 3) Inhibition of metastasis of B16 melanoma cells to the lungs of mice, 4) Increase in the average value of Young's moduli, i.e., cell stiffness, for human lung cancer cell lines and inhibition of cell motility and 5) Synergistic enhancement of anticancer activity against human cancer cell lines with the combination of EGCG and anticancer compounds. In the second part, we became interested in cancer stem cells (CSCs). 1) Cancer stem cells in mouse skin carcinogenesis by way of introduction, after which we discuss two subjects from our review on human CSCs reported by other investigators gathered from a search of PubMed, 2) Expression of stemness markers of human CSCs compared with their parental cells, and 3) EGCG decreases or increases the expression of mRNA and protein in human CSCs. On this point, EGCG inhibited self-renewal and expression of pluripotency-maintaining transcription factors in human CSCs. Human CSCs are thus a target for cancer prevention and treatment with EGCG and green tea catechins.
MeSH term(s)	Animals ; Catechin/analogs & derivatives ; Catechin/therapeutic use ; Cell Movement/drug effects ; Clinical Trials as Topic ; Humans ; Mice ; Neoplasms/pathology ; Neoplasms/prevention & control ; Neoplastic Stem Cells/drug effects ; Phytotherapy/methods ; Phytotherapy/trends ; Tea/chemistry
Chemical Substances	Tea ; Catechin (8R1V1STN48) ; epigallocatechin gallate (BQM438CTEL)
Language	English
Publishing date	2018-01-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1148964-9
ISSN	0219-1032 ; 1016-8478
ISSN (online)	0219-1032
ISSN	1016-8478
DOI	10.14348/molcells.2018.2227
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