Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion

• DOI: 10.1186/s13046-014-0070-0
• Publication Date: 2014-09-01T20:00:15Z
• Authors: Juan Li; Jie Liu; Pingping Li; Xiaona Mao; Wenjie Li; Jin Yang; Peijun Liu
• Keywords: Cell polarity; Polarity (international relations)

LKB1, also known as STK11, is a master kinase that serves an energy metabolic sensor and involved in cell polarity regulation. Recent studies have indicated LKB1 related to breast tumorigenesis cancer progression. However, little work has been done on the roles of epithelial-mesenchymal transition cancer. In this study, we tried prove loss disrupts epithelial causes tumor metastasis invasion.The relationships expression clinic-pathological parameters markers E-cadherin high-molecular-weight -cytokeratin (HMW-CK) were investigated 80 clinical tissue samples their paired normal control by using immunohistochemistry. Then, expressions metastatic non-metastatic lines compared. The determined immunofluorescence, western blot assay, migration invasive assays. Finally, non-transformed human line MCF-10A was cultured three dimensions further reveal role maintenance.Histopathological analysis showed level significantly negatively correlated with TNM stage, positively ER/PR status levels HMW-CK. Immunofluorescence staining co-localized at adheren junctions. vitro revealed enhanced migration, invasion acquisition mesenchymal phenotype, while overexpression MDA-MB-435 s cells, which low basal expression, promoted phenotype. it found for first time endogenous knockdown resulted abnormal acini formed cells grown 3D culture.Our data associated established unfavorable prognosis, such ER/PR, Knockdown gave rise dysregulation phenotype cells.