Abstract
The small GTPases of the Ras and Rho families are widely involved in tumorigenesis and metastasis. We recently showed that YM529/ONO-5920, a new developed bisphosphonate, inhibits the mevalonate pathway, is required for the prenylation of the small GTPases. In this study, we investigated whether YM529/ONO-5920 inhibits tumor cell migration, invasion, adhesion, and metastasis in B16BL6 cells, a mouse melanoma cell line. It was found that YM529/ONO-5920 significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not show anti-proliferative effects on B16BL6 cells. YM529/ONO-5920 also inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs). Furthermore, YM529/ONO-5920 suppressed Rho activation, but not activation of Ras. The results indicate that YM529/ONO-5920 suppresses the Rho/ROCK pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion and metastasis. These findings suggest that YM529/ONO-5920 has potential clinical applications for the treatment of tumour cell metastasis.
References
May 30, 1997·The Journal of Biological Chemistry·D B WhyteJ K Pai
Feb 5, 1998·Experimental Dermatology·V M Kähäri, U Saarialho-Kere
Oct 21, 1998·Oncogene·S L CampbellC J Der
Nov 18, 1998·Current Opinion in Cell Biology·M JohnsenK Danø
Jul 27, 1999·The Journal of Biological Chemistry·H Nagase, J F Woessner
Jul 28, 1999·Bone·R G Russell, M J Rogers
Feb 5, 2000·World Journal of Surgery·K DalbergM Bäckdahl
May 4, 2001·FEBS Letters·L VincentC Soria
May 18, 2001·Nature·L A Liotta, E C Kohn
Jul 27, 2001·Journal of Mammary Gland Biology and Neoplasia·S Malaney, R J Daly
Aug 15, 2001·Biological Chemistry·K DankerR Horstkorte
Mar 29, 2002·Cancer·Lisa A Di NezzaLois A Salamonsen
Apr 30, 2002·International Journal of Cancer. Journal International Du Cancer·Pia Vihinen, Veli-Matti Kähäri
Dec 13, 2002·Nature·Sandrine Etienne-Manneville, Alan Hall
Mar 29, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Zhaoxia LuanAndrew C Newby
Apr 19, 2003·Experimental Dermatology·E Kerkelä, U Saarialho-Kere
May 29, 2003·British Journal of Cancer·C DenoyelleC Soria
Sep 19, 2003·Life Sciences·Shozo NishidaKiyohiro Irimajiri
Oct 7, 2003·Oncogene·Thomas Bogenrieder, Meenhard Herlyn
Mar 18, 2004·The Journal of Gene Medicine·Eigo SuyamaKazunari Taira
Oct 14, 2004·Journal of Cellular Physiology·M LeabuB M C Chan
Dec 22, 2004·The Journal of Biological Chemistry·Hua Zhou, Randall H Kramer
Apr 22, 2005·Biological Chemistry·Klaudia Giehl
Jun 30, 2005·Cancer Metastasis Reviews·Silke KuphalAnja-Katrin Bosserhoff
Nov 22, 2005·Journal of Hepatology·Akira WadaNorio Hayashi
Jan 7, 2006·Cancer Research·Rubén A BartoloméJoaquin Teixidó
Feb 3, 2006·Cancer Research·Catherine C ParkMina J Bissell
Apr 26, 2006·Laboratory Investigation; a Journal of Technical Methods and Pathology·Nobuyuki HonmaYutaka Aoyagi
Jul 11, 2006·FEBS Letters·Bo LiYu-Hua Chen
Sep 16, 2006·European Journal of Pharmacology·Mayte PozoJesús González-Cabrero
Nov 24, 2006·Molecular Cancer Therapeutics·Sang-Oh YoonAn-Sik Chung
Jan 24, 2007·Biochemical and Biophysical Research Communications·Kae HashimotoTadashi Kimura
Jul 20, 2007·Clinical & Experimental Metastasis·Masanobu TsubakiShozo Nishida
Feb 6, 2008·IET Systems Biology·K L YeeD A Hammer
Feb 22, 2008·Recent Patents on Anti-cancer Drug Discovery·Roy BlumYoel Kloog
Oct 17, 2008·Cancer Research·Bharat JoshiIvan R Nabi
Citations
Oct 25, 2011·Journal of the National Cancer Institute·Gad Rennert
Sep 17, 2010·Journal of Experimental & Clinical Cancer Research : CR·Yasuhiro KideraShozo Nishida
Feb 5, 2014·Journal of Biomedical Science·Masanobu TsubakiShozo Nishida
Feb 22, 2012·Expert Opinion on Biological Therapy·Julie R NangiaMeghana V Trivedi
Nov 21, 2012·The Journal of Surgical Research·Hassan AlbadawiMichael T Watkins
Feb 14, 2012·Toxicology and Applied Pharmacology·Masanobu TsubakiShozo Nishida
May 15, 2012·Molecular and Cellular Endocrinology·Masanobu TsubakiShozo Nishida
Oct 23, 2012·Biochemical Pharmacology·Masanobu TsubakiShozo Nishida
Nov 3, 2016·Clinical and Experimental Pharmacology & Physiology·Masanobu TsubakiShozo Nishida
Mar 6, 2019·Journal of Cellular Physiology·Masanobu TsubakiShozo Nishida
Jun 2, 2020·Oncotarget·Maryam Zamanian-DaryoushJoseph A DiDonato
Aug 10, 2011·Current Opinion in Supportive and Palliative Care·James R Berenson
May 29, 2018·Cancer Metastasis Reviews·József TímárE Rásó
Sep 30, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gad RennertHedy S Rennert
Jul 30, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Graziella Ribeiro de SousaMaría Sol Brassesco