Abstract
Abstract Nucleolin, expressed in various cellular compartments, participates in DNA transcription, ribosomal biogenesis, regulation of RNA stability. It is evidence that the posttranslational cleavage of nucleolin determine the fate of cells, apoptosis or proliferation. However, the contributions of nucleolin accumulation and cleavage to tumor development are still not clear. Herein we found that nucleolin was dramatically increased in lung cancer and correlated with poor prognosis. The overexpressed nucleolin was cleaved to the smaller fragment (55 kDa), identified in human lung cancer and mouse models of lung cancer. To study the activated mechanism found that EGF-mediated EGFR and KRAS activations could enhance nucleolin expression through increasing Sp1-mediated transcription. Furthermore, to clarify the cleavage residue and cutting enzyme found that nucleolin could be cleaved at 255th Asp by MMP7 (255-710 a.a., TNCL). By using overexpression of TNCL indicated that TNCL enhanced proliferation and metastasis in vitro and in vivo. To further clarify the mechanism of TNCL-enhanced tumor malignancy show that TNCL significantly increase several oncogenes expression including MMP9, Alk and CD74 through associating with 3′-UTR to enhance mRNA stability. Taken together, MMP7 can cleave nucleolin to increase the oncogenes expression, leading lung cancer formation Citation Format: Jan-Jong Hung, Wen-Chang Chang. MMP7-mediated cleavage of nucleolin at the Asp255 induces MMP9 expression to promote tumor malignancy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2089. doi:10.1158/1538-7445.AM2014-2089
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.