Unknown

Dataset Information

0

Targeting RAS-driven human cancer cells with antibodies to upregulated and essential cell-surface proteins.


ABSTRACT: While there have been tremendous efforts to target oncogenic RAS signaling from inside the cell, little effort has focused on the cell-surface. Here, we used quantitative surface proteomics to reveal a signature of proteins that are upregulated on cells transformed with KRASG12V, and driven by MAPK pathway signaling. We next generated a toolkit of recombinant antibodies to seven of these RAS-induced proteins. We found that five of these proteins are broadly distributed on cancer cell lines harboring RAS mutations. In parallel, a cell-surface CRISPRi screen identified integrin and Wnt signaling proteins as critical to RAS-transformed cells. We show that antibodies targeting CDCP1, a protein common to our proteomics and CRISPRi datasets, can be leveraged to deliver cytotoxic and immunotherapeutic payloads to RAS-transformed cancer cells and report for RAS signaling status in vivo. Taken together, this work presents a technological platform for attacking RAS from outside the cell.

SUBMITTER: Martinko AJ 

PROVIDER: S-EPMC5796798 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC5341332 | BioStudies
| S-EPMC4350937 | BioStudies
1000-01-01 | S-EPMC4200232 | BioStudies
1000-01-01 | S-EPMC4791263 | BioStudies
1000-01-01 | S-EPMC3033256 | BioStudies
2019-01-01 | S-EPMC6756049 | BioStudies
2014-01-01 | S-EPMC4122376 | BioStudies
1000-01-01 | S-EPMC3234987 | BioStudies
2020-01-01 | S-EPMC7019151 | BioStudies
2014-01-01 | S-EPMC3931462 | BioStudies