| First Author | Nayak D | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 5 | Pages | 104193 |
| PubMed ID | 35479410 | Mgi Jnum | J:332306 |
| Mgi Id | MGI:7266084 | Doi | 10.1016/j.isci.2022.104193 |
| Citation | Nayak D, et al. (2022) EMT alterations in the solute carrier landscape uncover SLC22A10/A15 imposed vulnerabilities in pancreatic cancer. iScience 25(5):104193 |
| abstractText | The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) alpha and gamma signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNalpha/gamma-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human PDAC. |
