Oncogenic effect of PHLDB2 is associated with epithelial–mesenchymal transition and E-cadherin regulation in colorectal cancer

BACKGROUND: Pleckstrin Homology Like Domain Family Member 2 (PHLDB2) is an important protein with a PH-domain for interaction with partners to regulate cell migration. However, the role of PHLDB2 in human cancer metastasis, especially in colon cancer, still remains elusive. METHODS: The RNA-seq and clinical data of colorectal cancer patients from the Cancer Genome Atlas (TCGA) were analyzed for correlations between PHLDB2 and clinical outcomes as well as epithelial–mesenchymal transition (EMT) markers. Wound healing and transwell invasion assays were used to determine the effects of PHLDB2 on cell migration and invasiveness. Western blot and qRT-PCR analyses were employed to detect protein and mRNA changes, respectively. Co-immunoprecipitation was performed to assess protein–protein interaction. RESULTS: In the present report, by following our previous study, we found that PHLDB2 expression is associated with poorer prognosis, including disease-free survival, tumor stage, nodes pathology, as well as lymphatic and vascular invasion through TCGA data analysis. In addition, PHLDB2 expression is highly correlated with multiple epithelial–mesenchymal transition (EMT) markers involving cell-surface proteins (N-cadherin and OB-cadherin), cytoskeletal markers (α-SMA and Vimentin), ECM proteins (Fibronectin and Laminin 5), and transcription factors (Snail2, ZEB1, and Ets-1). We also demonstrated that PHLDB2 knockdown mediated by siRNA was sufficient to attenuate colon cancer cell migration and invasion, as well as E-Cadherin reduction, by TGF-β treatment. Interestingly, PHLDB2 expression levels were significantly elevated in response to EMT induction by TGF-β and EGF. Moreover, we found that PHLDB2 could bind to MDM2 and facilitate MDM2-mediated E-Cadherin degradation. CONCLUSIONS: Our findings suggest that PHLDB2 is a downstream effector of EMT pathway and may present as an important biomarker for colon cancer prognosis and a target for colon cancer intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0903-1) contains supplementary material, which is available to authorized users.