CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC

Molecular Therapy: Oncolytics

Xiaoyan Wang¹  Jiaxian Zhu¹  Yidan Ma²  Zuguo Li²  Lingfang Gao³  Yan Zhong⁴  Zhiyan Hu⁴  Ting Long⁵ 

[1] Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China;Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, 510515 Guangdong Province, P.R. China;The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China;Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China;Department of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101 Guangdong Province, P.R. China;

关键词: CIP4;    Cdc42;    NF-κB;    invadopodia;    colorectal cancer;    invasion;   

DOI  :  

来源: DOAJ

【 摘 要 】

Cdc42-interacting protein 4 (CIP4), a member of the F-BAR family, which plays an important role in regulating cell membrane and actin, has been reported to interact with Cdc42 and be closely associated with tumor invadopodia formation. In this study, we found that CIP4 expression was significantly higher in human CRC tissues and correlated with the CRC infiltrating depth and metastasis, as well as the lower survival rate in patients. In cultured CRC cells, knockdown of CIP4 inhibited cell migration and invasion ability in vitro and tumor metastasis in vivo, while the overexpression of CIP4 promoted invadopodia formation and matrix degradation ability. We then identified GTP-Cdc42 as a directly interactive protein of CIP4, which was upregulated and recruited by CIP4. Furthermore, activated NF-κB signaling pathway was found in CIP4 overexpression of CRC cells contributing to invadopodia formation, while the inhibition of either CIP4 or Cdc42 led to the suppression of the NF-κB pathway and resulted in a decreased quantity of invadopodia. Our findings suggested that CIP4 targets to recruit GTP-Cdc42 and directly combines with it to accelerate invadopodia formation and function by activating NF-κB signaling pathway, thus promoting CRC infiltration and metastasis.

【 授权许可】

Unknown