Journal article
Abstract 105: CADM1 is a TWIST1-regulated suppressor of melanoma invasion and survival
Cancer research (Chicago, Ill.), v 78(13_Supplement), pp 105-105
01 Jul 2018
Abstract
Abstract
Metastatic melanoma is the deadliest form of skin cancer; however, patients diagnosed and treated prior to metastatic dissemination have a good prognosis. The transcription factor, TWIST1 has been implicated in enhancing the migration and invasion of melanoma cells but the range of TWIST1-regulated targets is poorly described. In this study, we performed expression profiling to identify the TWIST1-regulated transcriptome. Gene ontology pathway analysis revealed that TWIST1 and epithelial to mesenchymal transition (EMT) were inversely correlated with levels of cell adhesion molecule 1 (CADM1). Chromatin immunoprecipitation (ChIP) studies and promoter assays demonstrated that TWIST1 physically interacts with the CADM1 promoter, suggesting TWIST1 directly represses CADM1 levels. Modulation of CADM1 resulted in significant effects on the migration and invasion of melanoma cells. In addition, elevated CADM1 elicited cell death in non-adherent conditions, an effect that could not be rescued with a pan-caspase inhibitor. Analyses suggest that CADM1 directed non-adherent cell death is associated with loss of mitochondrial membrane potential and subsequent failure of oxidative phosphorylation pathways. Furthermore, clinical data from TCGA indicates that CADM1 expression is correlated with better overall survival in patients. Together, these data suggest that CADM1 exerts tumor suppressive functions in melanoma by reducing invasive potential and may be a biomarker for improved survival of melanoma patients.
Citation Format: Edward J. Hartsough, Michele B. Weiss, Shea A. Heilman, Timothy J. Purwin, Curtis H. Kugel, Sheera R. Rosenbaum, Dan A. Erkes, Manoela Tiago, Inna Chervoneva, Andrew E. Aplin. CADM1 is a TWIST1-regulated suppressor of melanoma invasion and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 105.
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Details
- Title
- Abstract 105: CADM1 is a TWIST1-regulated suppressor of melanoma invasion and survival
- Creators
- Edward J. HartsoughMichele B. WeissShea A. HeilmanTimothy J. PurwinCurtis H. KugelSheera R. RosenbaumDan A. ErkesManoela TiagoInna ChervonevaAndrew E. Aplin
- Publication Details
- Cancer research (Chicago, Ill.), v 78(13_Supplement), pp 105-105
- Publisher
- American Association for Cancer Research (AACR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000468818901180
- Other Identifier
- 991020531939804721
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- Web of Science research areas
- Oncology