Abstract
BackgroundPleckstrin 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.MethodsThe 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.ResultsIn 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.ConclusionsOur 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.
Highlights
Pleckstrin Homology Like Domain Family Member 2 (PHLDB2) is an important protein with a PHdomain for interaction with partners to regulate cell migration
The same analysis does not show significant difference in perineural invasion, there is still a trend of elevated expression of PHLDB2 in perineural invasion indicator positive patients (Fig. 2c). These results indicate that high level of PHLDB2 is associated with poorer clinical a Disease free survival
Our present study revealed the important role of PHLDB2 in clinical outcomes and epithelial–mesenchymal transition (EMT) from a large cohort of colorectal patients, and provide the rationale to determine PHLDB2 as a valuable biomarker and/or to develop strategies to target PHLDB2 for colorectal cancer intervention
Summary
Pleckstrin Homology Like Domain Family Member 2 (PHLDB2) is an important protein with a PHdomain for interaction with partners to regulate cell migration. PHLDB2 is a PH domain-containing protein that plays an important role in mediating cell migration by forming complex with its partners, such as CLASPS, Prickle 1 and Liprin α1 [1,2,3]. In association with its client proteins, PHLDB2 is required for focal adhesion disassembly and cell polarization and migration [1,2,3]. Recent studies have demonstrated a critical role of epithelial–mesenchymal transition (EMT) in conferring metastatic traits on cancer cells by facilitating the ability of migrating, invading, and resisting therapies [4, 5]. Better understanding of EMT associated molecular events would provide promising opportunities to develop strategies for improving cancer prognosis and therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
