CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

BACKGROUND: Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. METHODS: We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. RESULTS: Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and αv-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. CONCLUSION: These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis

An ON-type direction selective ganglion cell in primate retina

<p>To maintain a stable and clear image of the world, our eyes reflexively follow the direction in which a visual scene is moving. Such gaze stabilisation mechanisms reduce image blur as we move in the environment. In non-primate mammals, this behaviour is initiated by retinal output neurons called ON-type direction-selective ganglion cells (ON-DSGCs), which detect the direction of image motion and transmit signals to brainstem nuclei that drive compensatory eye movements. However, in primates, ON-DSGCs have not yet been identified in the retina, raising the possibility that this reflex is mediated by cortical visual areas. Here, we mined single-cell RNA transcriptomic data from primate retina to identify a candidate ON-DSGC. We then combined two-photon calcium imaging, molecular identification, and morphological analysis, to reveal a population of ON-DSGCs in the macaque retina. The morphology, molecular signature, and GABAergic mechanisms that underlie direction selectivity in primate ON-DSGCs are highly conserved with lower mammals. We further show that the human retina contains a homologous cell type.  The presence of ON-DSGCs in primates highlights the need to examine the contribution of subcortical retinal mechanisms to normal and aberrant gaze stabilisation in the developing and mature visual system. </p><p>Funding provided by: National Eye Institute<br>Crossref Funder Registry ID: https://ror.org/03wkg3b53<br>Award Number: EY024265</p><p>Funding provided by: Hellman Family Foundation<br>Crossref Funder Registry ID: http://dx.doi.org/10.13039/100020111<br>Award Number: </p><p>Funding provided by: Glaucoma Research Foundation<br>Crossref Funder Registry ID: https://ror.org/05ez53b31<br>Award Number: </p&gt