| First Author | Kim JW | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 12 | Pages | 105603 |
| PubMed ID | 36483011 | Mgi Jnum | J:331881 |
| Mgi Id | MGI:7407782 | Doi | 10.1016/j.isci.2022.105603 |
| Citation | Kim JW, et al. (2022) DLL3 regulates Notch signaling in small cell lung cancer. iScience 25(12):105603 |
| abstractText | Tumor heterogeneity plays a critical role in tumor development and response to treatment. In small-cell lung cancer (SCLC), intratumoral heterogeneity is driven in part by the Notch signaling pathway, which reprograms neuroendocrine cancer cells to a less/non-neuroendocrine state. Here we investigated the atypical Notch ligand DLL3 as a biomarker of the neuroendocrine state and a regulator of cell-cell interactions in SCLC. We first built a mathematical model to predict the impact of DLL3 expression on SCLC cell populations. We next tested this model using a single-chain variable fragment (scFv) to track DLL3 expression in vivo and a new mouse model of SCLC with inducible expression of DLL3 in SCLC tumors. We found that high levels of DLL3 promote the expansion of a SCLC cell population with lower expression levels of both neuroendocrine and non-neuroendocrine markers. This work may influence how DLL3-targeting therapies are used in SCLC patients. |
