Down expression of LRP1B promotes cell migration via R ho A / C dc42 pathway and actin cytoskeleton remodeling in renal cell cancer
Author(s) -
Ni Shaobin,
Hu Jianran,
Duan Yongshun,
Shi Shuliang,
Li Ruo,
Wu Hongjin,
Qu Youpeng,
Li Yu
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12157
Subject(s) - rhoa , cdc42 , actin cytoskeleton , carcinogenesis , cell migration , biology , microbiology and biotechnology , lrp1b , cancer research , cell , chemistry , cytoskeleton , cancer , actin , ldl receptor , signal transduction , biochemistry , lipoprotein , cholesterol , genetics
The low‐density lipoprotein receptor‐related protein 1B ( LRP 1B) is known as a putative tumor suppressor. The decreased expression of LRP 1B has been involved in multiple primary cancers in several studies. However, its expression and function in the carcinogenesis of renal cell cancer ( RCC ) remain unclear. In this study, we investigated the expression of LRP 1B in RCC by in situ hybridization ( ISH ) and real‐time polymerase chain reaction ( qRT‐PCR ). Our results indicated that LRP 1B was frequently downexpressed in human RCC tissue and cell lines, which involved both epigenetic events ( DNA methylation and histone deacetylation) and N‐terminal deletion of LRP 1B . Moreover, we testified that knockdown of LRP 1B by sh RNA significantly promoted anchorage‐independent growth, cell migration and invasion in HEK 293 cells and renal cancer cells 127 in vitro . We further found that silencing of LRP 1B altered the expression of focal adhesion complex‐associated proteins, and Cdc42/RhoA activities, which regulate the cytoskeleton dynamics. Taken together, these results strongly support that LRP 1B may function as a tumor suppressor against renal cell cancer, and may regulate cell motility via RhoA/Cdc42 pathway and actin cytoskeleton reorganization in RCC .