Down expression of <scp><i>LRP1B</i></scp> promotes cell migration via <scp>R</scp>ho<scp>A</scp>/<scp>C</scp>dc42 pathway and actin cytoskeleton remodeling in renal cell cancer

<jats:p>The low‐density lipoprotein receptor‐related protein 1B (<jats:styled-content style="fixed-case">LRP</jats:styled-content>1B) is known as a putative tumor suppressor. The decreased expression of <jats:italic><jats:styled-content style="fixed-case">LRP</jats:styled-content>1B</jats:italic> has been involved in multiple primary cancers in several studies. However, its expression and function in the carcinogenesis of renal cell cancer (<jats:styled-content style="fixed-case">RCC</jats:styled-content>) remain unclear. In this study, we investigated the expression of <jats:italic><jats:styled-content style="fixed-case">LRP</jats:styled-content>1B</jats:italic> in <jats:styled-content style="fixed-case">RCC</jats:styled-content> by <jats:italic>in situ</jats:italic> hybridization (<jats:styled-content style="fixed-case">ISH</jats:styled-content>) and real‐time polymerase chain reaction (<jats:styled-content style="fixed-case">qRT‐PCR</jats:styled-content>). Our results indicated that <jats:italic><jats:styled-content style="fixed-case">LRP</jats:styled-content>1B</jats:italic> was frequently downexpressed in human <jats:styled-content style="fixed-case">RCC</jats:styled-content> tissue and cell lines, which involved both epigenetic events (<jats:styled-content style="fixed-case">DNA</jats:styled-content> methylation and histone deacetylation) and N‐terminal deletion of <jats:italic><jats:styled-content style="fixed-case">LRP</jats:styled-content>1B</jats:italic>. Moreover, we testified that knockdown of <jats:styled-content style="fixed-case">LRP</jats:styled-content>1B by sh<jats:styled-content style="fixed-case">RNA</jats:styled-content> significantly promoted anchorage‐independent growth, cell migration and invasion in <jats:styled-content style="fixed-case">HEK</jats:styled-content>293 cells and renal cancer cells 127 <jats:italic>in vitro</jats:italic>. We further found that silencing of <jats:italic><jats:styled-content style="fixed-case">LRP</jats:styled-content>1B</jats:italic> 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 <jats:styled-content style="fixed-case">LRP</jats:styled-content>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 <jats:styled-content style="fixed-case">RCC</jats:styled-content>.</jats:p>