Abstract
The scaffold protein syntenin abounds during fetal life where it is important for developmental movements. In human adulthood, syntenin gain-of-function is increasingly associated with various cancers and poor prognosis. Depending on the cancer model analyzed, syntenin affects various signaling pathways. We previously have shown that syntenin allows syndecan heparan sulfate proteoglycans to escape degradation. This indicates that syntenin has the potential to support sustained signaling of a plethora of growth factors and adhesion molecules. Here, we aim to clarify the impact of syntenin loss-of-function on cancer cell migration, growth, and proliferation, using cells from various cancer types and syntenin shRNA and siRNA silencing approaches. We observed decreased migration, growth, and proliferation of the mouse melanoma cell line B16F10, the human colon cancer cell line HT29 and the human breast cancer cell line MCF7. We further documented that syntenin controls the presence of active β1 integrin at the cell membrane and G1/S cell cycle transition as well as the expression levels of CDK4, Cyclin D2, and Retinoblastoma proteins. These data confirm that syntenin supports the migration and growth of tumor cells, independently of their origin, and further highlight the attractiveness of syntenin as potential therapeutic target.
Highlights
Syntenin is strongly expressed during human fetal life and at relatively low levels in adult tissues (Zimmermann et al, 2001)
Syntenin is a scaffold protein containing two Post synaptic density-95, Disc-large tumor suppressor and Zonula occludens1 (PDZ) domains that we originally identified as an intracellular adaptor for the syndecan family of heparan sulfate (HS) proteoglycans (Grootjans et al, 1997)
To generate cell populations stably depleted for syntenin, we used retroviralmediated gene transduction of small hairpin RNAs
Summary
Syntenin is strongly expressed during human fetal life and at relatively low levels in adult tissues (Zimmermann et al, 2001). Loss-of-function studies in Xenopus and zebrafish indicated that syntenin plays an important role in early developmental movements by controlling the noncanonical Wnt-signaling pathway (Luyten et al, 2008; Lambaerts et al, 2012), among others. Syntenin is detectable in adult human tissues, but an increasing number of independent studies indicate that syntenin is overexpressed in various patient tumor samples. Syntenin gainof-function was first described in metastatic melanoma (Helmke et al, 2004), and more recently in breast cancer (Qian et al, 2013; Yang et al, 2013) and in multiple neuroepithelial tumors (Kegelman et al, 2014) suggesting that syntenin could be a tumor marker.
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