Cysteine-rich intestinal protein 2 (CRIP2) acts as a repressor of NF-κB-mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis

Arthur Kwok Leung Cheung, Josephine M. Y. Ko, Hong Lok Lung, Kwok Wah Chan, Eric J. Stanbridge, Eugene Zabarovsky, Takashi Tokino, Lisa Kashima, Toshiharu Suzuki, Dora Lai Wan Kwong, Daniel Chua, Sai Wah Tsao, Maria Li Lung*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

60 Citations (Scopus)

Abstract

Chromosome 14 was transferred into tumorigenic nasopharyngeal carcinoma and esophageal carcinoma cell lines by a microcell-mediated chromosome transfer approach. Functional complementation of defects present in the cancer cells suppressed tumor formation. A candidate tumor-suppressor gene, cysteine-rich intestinal protein 2 (CRIP2), located in the hot spot for chromosomal loss at 14q32.3, was identified as an important candidate gene capable of functionally suppressing tumor formation. Previous studies have shown that CRIP2 is associated with development. To date, no report has provided functional evidence supporting a role for CRIP2 in tumor development. The present study provides unequivocal evidence that CRIP2 can functionally suppress tumorigenesis. CRIP2 is significantly down-regulated in nasopharyngeal carcinoma cell lines and tumors. CRIP2 reexpression functionally suppresses in vivo tumorigenesis and angiogenesis; these effects are induced by its transcription-repressor capability. It interacts with the NF-κB/p65 to inhibit its DNA-binding ability to the promoter regions of the major proangiogenesis cytokines critical for tumor progression, including IL6, IL8, and VEGF. In conclusion, we provide compelling evidence that CRIP2 acts as a transcription repressor of the NF-κB–mediated proangiogenic cytokine expression and thus functionally inhibits tumor formation and angiogenesis.
Original languageEnglish
Pages (from-to)8390-8395
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number20
DOIs
Publication statusPublished - 17 May 2011
Externally publishedYes

Scopus Subject Areas

  • General

User-Defined Keywords

  • Antiangiogenesis
  • Transcription regulator

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