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Department of Cancer Cell Biology, University of Toyama

Department of Cancer Cell Biology
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, JAPAN  

List of Publications (Selected Articles)
   1) Cancer and Signal Transduction
   2) Cytochrome P450 and Drug Metabolism
1) Cancer and Signal Transduction
Kawasaki K., Sakimura A., Park C.M., Tomaru R., Ozawa T., Zhou Y., Narita K., Kishi H., Muraguchi A., and Sakurai H.:
Feedback control of ErbB2 via ERK-mediated phosphorylation of a conserved threonine in the juxtamembrane domain.

Sci. Rep.,
6: 31502, 2016. [Open Access]
Zhou Y., Yamada N., Tanaka T., Hori T., Yokoyma S., Hayakawa Y., Yano S., Fukuoka J., Koizumi K., Saiki I., and Sakurai H.:
Crucial roles of RSK in cell motility by catalysing serine phosphorylation of EphA2.
Nat. Commun., 6: 7679, 2015. [Open Access]
Sakurai H.:
Targeting of TAK1 in inflammatory disorders and cancer.
Trends Pharmacol. Sci., 30: 522-530, 2012. [Abstract]
Wolf A., Beuerlein K., Eckart C., Weiser H., Dickkopf B., Müller H., Sakurai H., and Kracht M.:
Identification and functional characterization of a novel phosphorylation sites in TAK1-binding protein (TAB) 1.
PLoS ONE, 6: e29256, 2011. [Abstract]
Refaat A., Zhou Y., Suzuki S., Takasaki I., Koizumi K., Yamaoka S., Tabuchi Y., Saiki I., and Sakurai H.:
Distinct roles of transforming growth factor-β-activated kinase 1 (TAK1)-c-Rel and interferon regulatory factor 4 (IRF4) pathways in human T cell lymphotropic virus 1-transformed T helper 17 cells producing interleukin-9.
J. Biol. Chem., 286: 21092-20199, 2011. [Abstract]
Mizumoto Y., Kyo S., Kiyono T., Takakura M., Nakamura M., Maida Y., Mori N., Bono Y., Sakurai H., and Inoue M.:
Activation of NF-κB is a novel target of KRAS-induced endometrial carcinogenesis.
Clin. Cancer Res., 17: 1341-1350, 2011. [Abstract]
Suzuki S., Zhou Y., Refaat A., Takasaki I., Koizumi K., Yamaoka S., Tabuchi Y., Saiki I., and Sakurai H.:
Human T cell lymphotropic virus 1 manipulates interferon regulatory signals by controlling the TAK1-IRF3 and IRF4 pathways.
J. Biol. Chem., 285: 4441-4446, 2010. [Abstract]
Sayama K., Yamamoto M., Shirakata Y., Hanakawa Y., Hirakawa S., Dai X., Tohyama M., Tokumaru S., Shin M.S., Sakurai H., Akira S., and Hashimoto K.:
E2 polyubiquitin-conjugating enzyme Ubc13 in keratinocytes is essential for epidermal integrity.
J. Biol. Chem., 285: 30042-30049, 2010. [Abstract]
Nishimura M., Shin M.S., Singhirunnusorn P., Suzuki S., Kawanishi M., Koizumi K., Saiki I., and Sakurai H.:
TAK1-mediated serine/threonine phosphorylation of epidermal growth factor receptor via p38/extracellular signal-regulated kinase: NF-κB-independent survival pathways in tumor necrosis factor alpha signaling.
Mol. Cell. Biol., 29: 5529-5539, 2009. [Abstract]
Yamazaki K., Gohda J., Kanayama A., Miyamoto Y., Sakurai H., Yamamoto M., Akira S., Hayashi H., Su B., and Inoue J.:
Two mechanistically and temporally distinct NF-κB activation pathways in IL-1 signaling.
Sci. Signal., 2: ra66, 2009. [Abstract]
Koizumi K., Saitoh, Y., Minami T., Tsuneyama K., Miyahara T., Nakayama T., Sakurai H., Takano Y., Nishimura M., Imai T., Yoshie O., and Saiki I.:
Role of CX3CL1/fractalkine in osteoclast differentiation and bone resorption.
J. Immunol., 183: 7825-7831, 2009. [Abstract]
Ueno Y., Sakurai H., Tsunoda S., Matsuo M., Choo M.K., Koizumi K., and Saiki I.:
Heregulin-induced activation of ErbB3 by EGFR tyrosine kinase activity promotes tumor growth and metastasis in melanoma cells.
Int. J. Cancer, 123: 340-347, 2008. [Abstract]
Singhirunnusorn P., Ueno Y., Matsuo M., Suzuki S., Saiki I., and Sakurai H.:
Transient suppression of ligand-mediated activation of epidermal growth factor receptor by tumor necrosis factor-α through the TAK1-p38 pathway.

J. Biol. Chem., 282: 12698.12706, 2007. [Abstract]
Suzuki S., Singhirunnusorn P., Mori A., Yamaoka S., Kitajima I., Saiki I., and Sakurai H.:
Constitutive activation of TAK1 by HTLV-1 Tax-dependent overexpression of TAB2 induces activation of JNK-ATF2, but not IKK-NF-κB.

J. Biol. Chem., 282: 25177-25181, 2007. [Abstract]
Shambharkar P.B., Blonska M., Pappu B.P., You Y., Sakurai H., Darnay B., and Lin X.:
Phosphorylation and ubiquitination of the IκB kinase complex by two distinct signaling pathways.

EMBO J., 26: 1794-1805, 2007. [Abstract]
Hojo S., Koizumi K., Tsuneyama K., Arita Y., Cui Z., Shinohara K., Minami T., Hashimoto I., Nakayama T., Sakurai H., Takano Y., Yoshie O., Tsukada K., and Saiki I.:
High level expression of chemokine CXCL16 by tumor cells correlated with a good prognosis and increased tumor-infiltrating lymphocytes in colorectal cancer.

Cancer Res., 67: 4725-4731, 2007. [Abstract]
Choo M.K., Sakurai H., Koizumi K., and Saiki I.:
TAK1-mediated stress signaling pathways are essential for TNF-α-promoted pulmonary metastasis of murine colon cancer cells.
Int. J. Cancer, 118: 2758-2764, 2006. [Abstract]
Yasumoto K., Koizumi K., Kawashima A., Saitoh Y., Arita Y., Shinohara K. Minami T., Nakayama T., Sakurai H., Takahashi Y., Yoshie O., and Saiki I.:
Role of the CXCL12/CXCR4 axis in peritoneal carcinomatosis of gastric cancer.

Cancer Res., 66: 2181-2187, 2006. [Abstract]
Thiefes A., Wolf A., Grassl G.A., Doerrie A., Matsumoto K., Autenrieth I., Bohn E., Sakurai H., Niedenthal R., Resch K., and Kracht M.:
The Yersinia enterocolitica effector YopP inhibits host cell signalling by inactivating the protein kinase TAK1 in the IL-1 signalling pathway.
EMBO Rep.
, 7: 838-844, 2006. [Abstract]
Yamamoto M., Sato S., Saitoh T., Sakurai H., Uematsu S., Kawai T., Ishii K.J., Takeuchi O., and Akira S.:
Cutting Edge: Pivotal function of Ubc13 in thymocyte TCR signaling.
J. Immunol., 177: 7520-7524, 2006. [Abstract]
Yamamoto M., Okamoto Y., Takeda T., Sato S., Sanjo H., Uematsu S., Saitoh T., Yamamoto N., Sakurai H., Ishii K.J., Yamaoka S., Kawai T., Matsuura Y., Takeuchi O., and Akira S.:
Key function for the Ubc13 E2 ubiquitin-conjugating enzyme in immune receptor signaling.
Nat. Immunol., 7: 962-970, 2006. [Abstract]
Choo M.K., Kawasaki N., Singhirunnusorn P., Koizumi K., Sato S., Akira S., Saiki I., and Sakurai H.:
Blockade of transforming growth factor-β-activated kinase 1 activity enhances TRAIL-induced apoptosis through activation of a caspase cascade.
Mol. Cancer Ther., 5: 2970-2976, 2006. [Abstract]
Singhirunnusorn P, Suzuki S., Kawasaki N., Saiki I., and Sakurai H.:
Critical roles of threonine 187 phosphorylation in cellular stress-induced rapid and transient activation of transforming growth factor-β-activated kinase 1 (TAK1) in a signaling complex containing TAK1-binding protein TAB1 and TAB2.
J. Biol. Chem., 280: 7359-7368, 2005. [Abstract]
Ueno Y., Sakurai H., Matsuo M., Choo M.K., Koizumi K., and Saiki I.:
Selective inhibition of TNF-α-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib.
Br. J. Cancer, 92: 1690-1695, 2005. [Abstract]
Shinohara H., Yasuda T., Aiba Y., Sanjo H., Hamadate M., Watarai H., Sakurai H., and Kurosaki T.:
PKCβ regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1.
J. Exp. Med., 202: 1423-1431, 2005. [Abstract]
Blonska M., Shambharkar P.B., Kobayashi M., Zhang D., Sakurai H., Su B., and Lin X.:
TAK1 is recruited to the tumor necrosis factor-α (TNF-α) receptor 1 complex in a receptor-interacting protein (RIP)-dependent manner and cooperates with MEKK3 leading to NF-κB activation.
J. Biol. Chem., 280: 43056-43063, 2005. [Abstract]
Matsuo M., Sakurai H. and Saiki I.:
ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, shows antimetastatic activity using a hepatocellular carcinoma model.
Mol. Cancer Ther.,
2: 557-561, 2003. [Abstract]
Sakurai H., Suzuki S., Kawasaki N., Nakano H., Okazaki T., Chino A., Doi T. and Saiki I.:
Tumor necrosis factor-α-induced IKK phosphorylation of NF-κB p65 on serine 536 is medeated through the TRAF2, TRAF5 and TAK1 signaling pathway.
J. Biol. Chem.,
278, 36916-36923, 2003. [Abstract]
Fujita F., Delhase M., Taniguchi Y., Kato T., Narita Y., Furuya A., Ogawa T., Sakurai H., Joh T., Itoh M., Karin M. and Nakanishi M.:
Identification of NAP1: a regulatory subunit of IκB kinase-related kinases that potentiates NF-κB signaling.
Mol. Cell. Biol. , 23, 7780-7793, 2003. [Abstract]
Sizemore N., Lerner N., Dombrowski N., Sakurai H. and Stark G.R.:
Distinct Roles of the IκB kinase α and β subunits in liberating nuclear factor kB (NF-κB) from IκB and in phosphorylating the p65 subunit of NF-κB.

J. Biol. Chem., 277: 3863-3869, 2002. [Abstract]
Mizukami J., Takaesu G., Akatsuka H., Sakurai H. Ninomiya-Tsuji J., Matsumoto K.and Sakurai N.:
Receptor activator of NF-κB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase through a signaling complex containing TAK1, TAB2, and TRAF6.
Mol. Cell. Biol., 22: 992-1000, 2002. [Abstract]
Yang J., Fan G., Wadzinski B.E., Sakurai H., and Richmond A.:
Protein phosphatase 2A interacts with and directly dephosphorylates RelA.
J. Biol. Chem., 276: 1423-1431, 2001. [Abstract]
Sakurai H., Chiba H., Miyoshi H., Sugita T., and Toriumi W.
IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain.
J. Biol. Chem., 274: 30353-30356, 1999. [Abstract]
Sakurai H., Miyoshi H., Toriumi W., and Sugita T.:
Functional interactions of transforming growth factor β-activated kinase 1 with IκB kinases to stimulate NF-κB activation.
J. Biol. Chem., 274: 10641-10648, 1999. [Abstract]
Sakurai H., Shigemori N., Hasegawa K., and Sugita T.:
TGF-β-activated kinase 1 stimulates NF-κB activation by an NF-κB-inducing kinase-independent mechanism.
Biochem. Biophys. Res. Commun., 243: 545-549, 1998. [Abstract]

Cytochrome P450 and Drug Metabolism
Udomsuk L., Jarukamjorn K., Putalun W., Sakuma T., Kawasaki Y. and Nemoto N.:
Modified expression of aryl hydrocarbon receptor-related genes by deoxymiroestrol, a phytoestrogen, in mouse hepatocytes in primary culture.
J. Ethnopharmacol., 137: 902-908, 2011. [Abstract]
Bhadhprasit W., Sakuma T., Kawasaki Y. and Nemoto N.:
Hepatocyte nuclear factor 4 alpha regulates expression of the mouse female-specific Cyp3a41 gene in the liver.
Drug Metab. Dispos., Drug Metab Dispos. [Abstract]
Chatuphonprasert W., Kondo S., Jarukamjorn K., Kawasaki Y., Sakuma T. and Nemoto N.:
Potent modification of inducible CYP1A1 expression by flavonoids.
Biol. Pharm. Bull., 33: 1698?1703, 2010. [Abstract]
Kawasaki Y., Sakuma T., Goto Y. and Nemoto N.:
Regulatory xenobiotic responsive elements in the distal 5'-flanking region of the mouse Cyp1a2 gene required for transcriptional activation by 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Drug. Metab. Dispos., 38: 1640-1643, 2010. [Abstract]
Jarukamjorn K., Kondo S., Chatuphonprasert W., Sakuma T., Kawasaki Y. and Nemoto N.:
Gender-associated modulation of inducible CYP1A1 expression by andrographolide in mouse liver.
Eur. J. Pharm. Sci., 39: 394-401, 2010. [Abstract]
Hashita T., Sakuma T., Akada M., Nakajima A., Yamahara H., Ito S., Takesako H. and Nemoto N.:
Forkhead box A2-mediated regulation of female-predominant expression of the mouse Cyp2b9 gene.
Drug Metab. Dispos., 36: 1080-1087, 2008. [Abstract]
Sakuma T., Bhadhprasit W., Hashita T. and Nemoto N.:
Synergism of glucocorticoid hormone with growth hormone for female-specific mouse Cyp3a44 gene expression.
Drug Metab. Dispos., 36: 878-884, 2008. [Abstract]
Jaruchotikamol A., Jarukamjorn K., Sirisangtrakul W., Sakuma T., Kawasaki Y. and Nemoto N.:
Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes.
Toxicol. Appl. Pharmacol., 224: 156-162, 2007. [Abstract]
Bhadhprasit W., Sakuma T., Hatakeyama N., Fuwa M., Kitajima K. and Nemoto N.:
Involvement of glucocorticoid receptor and pregnane X receptor in the regulation of mouse CYP3A44 female-predominant expression by glucocorticoid hormone.
Drug Metab. Dispos., 35: 1880-1885, 2007. [Abstract]
Jarukamjorn K., Sakuma T., Jaruchotikamol A., Ishino Y., Oguro M. and Nemoto N.:
Modified expression of cytochrome P450 mRNAs by growth hormone in mouse liver.
Toxicology, 219: 97-105, 2006. [Abstract]
Sakuma T., Kitajima K., Nishiyama M., Mashino M., Hashita T. and Nemoto N.:
Suppression of female-specific murine Cyp2b9 gene expression by growth or glucocorticoid hormones.
Biochem. Biophys. Res. Commun., 323: 776-781, 2004. [Abstract]
Sakuma T., Kitajima K., Nishiyama M., Endo Y., Miyauchi K., Jarukamjorn K. and Nemoto N.:
Collaborated regulation of female-specific murine Cyp3a41 gene expression by growth and glucocorticoid hormones.
Biochem. Biophys. Res. Commun., 314: 495-500, 2004. [Abstract]
Uchida Y-I., Yano A., Kumakura S-I., Sakuma T. and Nemoto N.:
Enhancer elements in the mouse Cyp1a2 gene for constitutive expression.
Biochem. Biophys. Res. Commun., 297: 1297-1301, 2002. [Abstract]
Sakuma T., Endo Y., Mashino M., Kuroiwa M., Ohara A., Jarukamjorn K. and Nemoto N.:
Regulation of the expression of two female-predominant CYP3A mRNAs (CYP3A41 and CYP3A44) in mouse liver by sex and growth hormones.
Arch. Biochem. Biophys., 404: 234-242, 2002. [Abstract]
Sakuma T., Honma R., Maguchi S., Tamaki H. and Nemoto N.:
Different expression of hepatic and renal cytochrome P450s between streptozotocin-induced diabetic mice and rats.
Xenobiotica, 31: 223-237, 2001. [Abstract]
Jarukamjorn K., Sakuma T., Yamamoto M., Ohara A. and Nemoto N.:
Sex-associated expression of the mouse hepatic and renal CYP2B enzymes by glucocorticoid hormone.
Biochem. Pharmacol., 62: 161-169, 2001. [Abstract]
Sakuma T., Takai M., Endo Y., Kuroiwa M., Ohara A., Jarukamjorn K., Honma R. and Nemoto N.:
A novel female-specific member of the CYP3A subfamily in the mouse liver.
Arch. Biochem. Biophys., 377: 153-162, 2000. [Abstract]
Sakuma T., Ohtake M., Katsurayama Y., Jarukamjorn K. and Nemoto N.:
Induction of CYP1A2 by phenobarbital in the livers of arylhydrocarbon-responsive and -nonresponsive mice..
Drug Metab. Dispos., 27: 379-384,1999. [Abstract]