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ABSTRACT Connexin genes expressing gap junction proteins have tumor-suppressive effects on primary cancers with certain cell specificity, but the suppressive effects on metastatic cancers

are still conflicting. In this study, we show that connexin32 (Cx32) has a strong tumor-suppressive effect on a human metastatic renal cell carcinoma cell line (Caki-1 cell). Cx32 expression

in Caki-1 cells reduced _in vitro_ malignant phenotypes of the cells such as anchorage independency and invasion capacity. Furthermore, the Cx32 expression drastically reduced the

development of Caki-1 cells in nude mice. We also determined that Cx32 reduced the malignant phenotypes in Caki-1 cells mainly through the inactivation of Src signaling. Especially,

Cx32-dependent inactivation of Src decreased the production of vascular epithelial growth factor (VEGF) via the suppression of signal transducers and activators of transcription 3 (Stat3)

activation, and we confirmed this result using short interfering RNA. In nude mice, Cx32-transfected Caki-1 cells showed lower serum level of VEGF comparing mock transfectant, and the

development of the cells in nude mice positively related to the VEGF level. These data suggest that _Cx32_ acts as a tumor suppressor gene in Caki-1 cells and that the tumor-suppressive

effect partly depends on the inhibition of Src-Stat3-VEGF signal pathway. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS DOWNREGULATION OF SBF2-AS1 FUNCTIONS AS A TUMOR SUPPRESSOR IN

CLEAR CELL RENAL CELL CARCINOMA BY INHIBITING MIR-338-3P-TARGETED ETS1 Article 28 July 2020 INHIBITION OF PRIMARY CILIA-HEDGEHOG SIGNALING AXIS TRIGGERS AUTOPHAGIC CELL DEATH AND SUPPRESSES

MALIGNANT PROGRESSION OF VHL WILD-TYPE CCRCC Article Open access 10 October 2024 CIRCESRP1 INHIBITS CLEAR CELL RENAL CELL CARCINOMA PROGRESSION THROUGH THE CTCF-MEDIATED POSITIVE FEEDBACK

LOOP Article Open access 13 November 2021 REFERENCES * Bond SL, Bechberger JF, Khoo NK and Naus CC . (1994). _Cell Growth Differ._, 5, 179–186. * Bowman T, Garcia R, Turkson J and Jove R .

(2000). _Oncogene_, 19, 2474–2488. * Bromberg J and Darnell Jr JE . (2000). _Oncogene_, 19, 2468–2473. * Bromberg JF, Wrezeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C and Darnell

Jr JE . (1999). _Cell_, 98, 295–303. * Buettner R, Mora LB and Jove R . (2002). _Clin. Cancer Res._, 8, 945–954. * Cartwright CA, Meisler AI and Eckhart W . (1990). _Proc. Natl. Acad. Sci.

USA_, 87, 558–562. * Fittzgerald DJ and Yamasaki H . (1990). _Tetraog. Carcinog. Mutagen._, 10, 89–102. * Folkman J . (1995). _N. Engl. J. Med._, 333, 1757–1763. * Fujimoto E, Satoh H, Ueno

K, Nagashima Y, Hagiwara K, Yamasaki H and Yano T . (2004). _Mol. Carcinogenesis_, 40, 135–142. * Genda T, Sakamoto M, Ichida T, Asakura H and Hirihashi S . (2000). _Lab. Invest._, 80,

387–394. * Goodenough DA and Paul DL . (2003). _Nature Rev. Mol. Cell Biol._, 4, 285–294. * Grunstein J, Roberts WG, Mathieus-Costello O, Hanahan D and Johnson RS . (1999). _Cancer Res._,

59, 1592–1598. * Hirai A, Yano T, Nishikawa K, Suzuki K, Asano R, Satoh H, Hagiwara K and Yamasaki H . (2003). _Am. J. Nephrol._, 23, 172–177. * Holder JW, Elmore E and Barrett JC . (1993).

_Cancer Res._, 53, 3475–3485. * Irby RB and Yeatman TJ . (2000). _Oncogene_, 19, 5636–5642. * Karni R, Jove R and Levitzki A . (1999). _Oncogene_, 18, 4654–4662. * Korhonen M, Sariola H,

Could VE, Kangas L and Virtanen I . (1994). _Cancer Res._, 54, 4532–4538. * Laird AD, Li G, Moss KG, Blake RA, Broome MA, Cherrington LM and Mendel DB . (2003). _Mol. Cancer Ther._, 2,

461–469. * Mareel MM, Bracke ME, Van Roy F and de Baetselier P . (1997). _Encyl. Cancer_, 2, 1072–1083. * Martyn KD, Kurata WE, Warn-Cramer BJ, Burt JM, Tenbroek E and Lau AF . (1997). _Cell

Growth Differ._, 8, 1015–1027. * Mesnil M . (2002). _Biol. Cell_, 94, 493–500. * Motzer RJ, Bander NH and Nanus DM . (1996). _N. Engl. J. Med._, 335, 865. * Motzer RJ and Russo P . (2000).

_J. Urol._, 163, 408–417. * Nicolson GL, Dulski KM and Trosko JE . (1988). _Proc. Natl. Acad. Sci. USA_, 85, 473–476. * Niu G, Wright KL, Huang M, Song L, Haura E, Turkson J, Zhang S, Wang

T, Sinibaldi D, Coppola D, Heller R, Ellis LM, Karras J, Bromberg J, Pardoll D, Jove R and Yu H . (2002). _Oncogene_, 21, 2000–2008. * Omori Y and Yamasaki H . (1999). _Carcinogenesis_, 20,

1913–1918. * Paul DL . (1995). _Curr. Opin. Cell Biol._, 7, 665–672. * Rae RS, Mehta PP, Chang CC, Trsoko JE and Ruch RJ . (1998). _Mol. Carcinogenesis_, 22, 120–127. * Ren Z and Schaefer TS

. (2002). _J. Biol. Chem._, 277, 38386–38493. * Simpson JC, Rose B and Lowenstein WR . (1977). _Science_, 195, 294–296. * Sinibaldi D, Wharton W, Turkson J, Bowman T, Pledger WJ and Jove R

. (2000). _Oncogene_, 19, 5419–5427. * Stauffer KA, Kumar NM, Gilula NB and Unwin N . (1991). _J. Cell Biol._, 115, 141–150. * Trosko JE, Madhukar BV and Chang CC . (1993). _Life Sci._, 53,

1–19. * Turkson J and Jove R . (2000). _Oncogene_, 19, 6613–6626. * Wiener JR, Nakano K, Kruzelock RP, Bucana CD, Bast Jr RC and Gallick GE . (1999). _Clin. Cancer Res._, 5, 2164–2170. *

Willecke K, Eiberger J, Degen J, Eckardt D, Romualdi A, Guldenagel M, Deutsch U and Sohl G . (2002). _Biol. Chem._, 383, 725–737. * Yamasaki H and Naus CCG . (1996). _Carcinogenesis_, 17,

1199–1213. * Yano T, Blazquez FJH, Omori Y and Yamasaki H . (2001). _Carcinogenesis_, 22, 1593–1600. * Yano T, Ito F, Satoh H, Hagiwara K, Nakazawa H, Toma H and Yamasaki H . (2003). _Kidney

Int._, 63, 381. * Yano T and Yamasaki H . (2001). _Mol. Carcinogenesis_, 31, 101–109. * Yu H and Jove R . (2004). _Nature Rev. Cancer_, 4, 97–105. Download references ACKNOWLEDGEMENTS We

are grateful to Miss Haruna Satoh for her technical assistance. This work was supported by a grant on Health Sciences Focusing on Drug Innovation from the Japan Health Sciences Foundation

(SH24209 and KH 21012). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku,

162-8636, Tokyo, Japan Eriko Fujimoto, Hiromi Sato, Sumiko Shirai, Keiko Fukumoto, Hiromi Hagiwara, Kiyokazu Hagiwara & Tomohiro Yano * Faculty of Pharmaceutical Sciences, Chiba

University, 1-8-1 Inohana, Chuo, 260-8675, Chiba, Japan Eriko Fujimoto, Hiromi Sato, Etsuko Negishi & Koichi Ueno * Department of Pathology, Yokohama City University Medical School, 3-8

Fukuura, Kanazawa, 236-0004, Kanagawa, Japan Yoji Nagashima * Japan Human Sciences Foundation, 13-4 Nihonbashi-Kodenmacho, Chuo, 103-0001, Tokyo, Japan Hiromi Hagiwara * Department of

Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan Yasufumi Omori * Faculty of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda,

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Tomohiro Yano. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Fujimoto, E., Sato, H., Shirai, S. _et al._ Connexin32 as a tumor suppressor gene in a

metastatic renal cell carcinoma cell line. _Oncogene_ 24, 3684–3690 (2005). https://doi.org/10.1038/sj.onc.1208430 Download citation * Received: 21 April 2004 * Revised: 03 December 2004 *

Accepted: 06 December 2004 * Published: 14 March 2005 * Issue Date: 19 May 2005 * DOI: https://doi.org/10.1038/sj.onc.1208430 SHARE THIS ARTICLE Anyone you share the following link with will

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content-sharing initiative KEYWORDS * connexin32 * tumor suppressor gene * Src * VEGF * metastatic renal cell carcinoma