Document Type
Article
Publication Date
1-2026
Identifier
DOI: 10.1002/dvdy.70059
Abstract
BACKGROUND: Cell migration and invasion are well-coordinated in development and disease but remain poorly understood. We previously showed that the neural crest (NC) cell migratory wavefront shares a 45-gene panel with other cell invasion phenomena. To rapidly and systematically identify critical genes, we performed a high-throughput siRNA screen and statistical and deep learning analyses to determine changes in NC- versus non-NC-derived human cell line behaviors.
RESULTS: We find 14 out of 45 genes significantly reduced c8161 melanoma cell migration; four of the 14 genes altered leader cell motility (BMP4, ITGB1, KCNE3, and RASGRP1). Deep learning identified marked disruptions in cell-neighbor interactions after BMP4 or RASGRP1 knockdown in c8161 cells. Recombinant proteins added to the culture media revealed five out of the 11 known secreted molecules stimulated c8161 cell migration. BMP4 knockdown severely reduced c8161 in vivo invasion in a chick embryo transplant model. Addition of BMP4 protein to the culture media of BMP4-siRNA-treated c8161 cells rescued cell migratory ability.
CONCLUSION: High-throughput screening and deep learning distilled a 45-gene panel to a small subset of genes critical to melanoma and warrant deeper in vivo functional analysis for their role and potential synergies in driving NC cell migration and invasion.
Journal Title
Developmental dynamics : an official publication of the American Association of Anatomists
Volume
255
Issue
1
First Page
25
Last Page
42
MeSH Keywords
Neural Crest; Humans; Cell Movement; Melanoma; Neoplasm Invasiveness; Chick Embryo; Cell Line, Tumor; Animals; High-Throughput Screening Assays; Bone Morphogenetic Protein 4; Deep Learning; Gene Expression Regulation, Neoplastic
PubMed ID
40637615
Keywords
attention networks; cell invasion; deep learning; high‐throughput; melanoma; migration; neural crest; siRNA screen
Recommended Citation
Kasemeier-Kulesa JC, Martina Perez S, Baker RE, Kulesa PM. Identification of neural crest and melanoma cancer cell invasion and migration genes using high-throughput screening and deep attention networks. Dev Dyn. 2026;255(1):25-42. doi:10.1002/dvdy.70059
Comments
Grants and funding
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher's Link: https://anatomypubs.onlinelibrary.wiley.com/doi/10.1002/dvdy.70059