Subtype-specific secretomic characterization of pulmonary neuroendocrine tumor cells.
作者： Xu-Dong Wang , Rongkuan Hu , Qing Ding , Trisha K. Savage , Kenneth E. Huffman
DOI: 10.1038/S41467-019-11153-5
关键词:
摘要: Pulmonary neuroendocrine (NE) cancer, including small cell lung cancer (SCLC), is a particularly aggressive malignancy. The lineage-specific transcription factors Achaete-scute homolog 1 (ASCL1), NEUROD1 and POU2F3 have been reported to identify the different subtypes of pulmonary NE cancers. Using large-scale mass spectrometric approach, here we perform quantitative secretome analysis in 13 lines that signify subtypes. We quantify 1,626 proteins IGFBP5 as secreted marker for ASCL1High SCLC. ASCL1 binds E-box elements directly regulates its transcription. Knockdown decreases expression, which, turn, leads hyperactivation IGF-1R signaling. Pharmacological co-targeting results markedly synergistic effects SCLC vitro mouse models. expect this resource will provide foundation future mechanistic biomarker discovery studies, helping delineate molecular underpinnings tumors.
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