Functinal analysis of a novel gene involved in the progression of colorectal cancers

• Project/Area Number: 23501276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: NAGAYAMA satoshi 公益財団法人がん研究会, その他部局等, その他 (70362499)
• Co-Investigator(Kenkyū-buntansha): 戸口田 淳也 京都大学, 再生医科学研究所/iPS 細胞研究所, 教授/副所長 (40273502) ; 坂井 義治 京都大学, 医学(系)研究科(研究院), 教授 (60273455)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大腸癌 / 浸潤

Research Abstract

In this study, we found a marked elevation of AFAP1L1 gene expression in colorectal cancer (CRC) tissues as compared to the adjacent normal mucosa. Multivariate analysis revealed that AFAP1L1 was an independent and significant factor for the recurrence of rectal cancers. AFAP1L1-transduced CRC cells exhibited a rounded shape, increased cell motility on planar substrates, and resistance to anoikis in vitro. AFAP1L1 was identified as a novel associating partner of vinculin by immunoprecipitation assay. The local administration of a siRNA against AFAP1L1 significantly suppressed the in vivo tumor growth of xenografts, suggesting that AFAP1L1 might be a candidate therapeutic target for CRCs. These results suggest that AFAP1L1 plays a role in the progression of CRCs by modulating cell shape and motility and by inhibiting anoikis, presumably through interactions with vinculin-including protein complexes.

Research Products

• [Journal Article] AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers (2014)
  • Author(s): Ryo Takahashi, Satoshi Nagayama, Moritoshi Furu, Yoichiro Kajita, Tomohisa Kato, Seiya Imoto, Yoshiharu Sakai and Junya Toguchida
  • Journal Title: Cancer Medicine Volume: (in press)
• [Journal Article] AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers. (2014)
  • Author(s): Takahashi R, Nagayama S, Furu M, Kajita Y, Jin Y, Kato T, Imoto S, Sakai Y, Toguchida J.
  • Journal Title: Cancer Medicine Volume: なし Issue: 4 Pages: 759-774
  • DOI: 10.1002/cam4.237
  • Peer Reviewed
• [Presentation] 細胞骨格関連タンパクC7059は細胞形態および細胞遊走を制御し、大著癌進展に関与する (2014)
  • Author(s): 長山聡
  • Organizer: 日本外科学会
  • Place of Presentation: 京都
• [Presentation] 細胞骨格関連タンパクC7059 は細胞遊走能を制御して大腸癌進展に関与する (2013)
  • Author(s): 長山聡、高橋亮、井元清哉、布留守敏、梶田洋一郎、片桐豊雅、中村祐輔、坂井義治、戸口田淳也
  • Organizer: 第72回日本癌学会
  • Place of Presentation: (英語口演)
• [Presentation] 細胞骨格関連タンパクC7059 は細胞形態,遊走能および浸潤仮足形成を制御し,大腸癌進展に関与する (2013)
  • Author(s): 高橋亮、長山聡、布留守敏、梶田洋一郎、大越香江、山田理大、河田健二、長谷川傑、戸口田淳也、坂井義浩
  • Organizer: 第68回日本消化器外科学会
• [Presentation] アクチン骨格関連タンパクC7059 は細胞遊走能および浸潤仮足(invadopodia)形成を制御し,大腸癌進展に関与する (2013)
  • Author(s): 高橋 亮、長山 聡、布留 守敏、梶田 洋一郎、村上 哲平、加藤 滋、久森 重夫、山田 理大、大越 香江、角田 茂、田中 英治、河田 健二、小濱 和貴、長谷川 傑、岡部 寛、戸口田 淳也、坂井 義治
  • Organizer: 第113回日本外科学会