LKB1 obliterates Snail stability and inhibits pancreatic cancer metastasis in response to metformin treatment.

ABSTRACT: Metastasis to distant organs is a particularly ominous feature of malignant cancer. LKB1 (also known as STK11) has been identified as a tumor suppressor in several types of cancers. Here, we show that LKB1 is at low levels and is negatively associated with poor clinical outcomes in pancreatic cancer (PC). LKB1 is inversely correlated with Snail protein in PC, in which the loss of LKB1 facilitates metastasis through elevating Snail protein level. Furthermore, LKB1 boosts Snail's interaction with E3 ligase FBXL14, leading to increasing ubiquitin-mediated Snail degradation. Notably, metformin could increase Snail protein ubiquitination via augmenting the location of LKB1 at cytoplasm as well as increasing LKB1 expression. Altogether, our data established that LKB1 impedes invasion and metasta

SUBMITTER: Song L 

PROVIDER: S-EPMC5980291 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature