Cell invasion through basement membrane is a specialized cellular behavior 
critical for many developmental processes and leukocyte trafficking. Invasive 
cellular behavior is also inappropriately co-opted during cancer progression. 
Acquisition of an invasive phenotype is accompanied by changes in gene 
expression that are thought to coordinate the steps of invasion. The 
transcription factors responsible for these changes in gene expression, however, 
are largely unknown. C. elegans anchor cell (AC) invasion is a genetically 
tractable in vivo model of invasion through basement membrane. AC invasion 
requires the conserved transcription factor FOS-1A, but other transcription 
factors are thought to act in parallel to FOS-1A to control invasion. Here we 
identify the transcription factor HLH-2, the C. elegans ortholog of Drosophila 
Daughterless and vertebrate E proteins, as a regulator of AC invasion. Reduction 
of HLH-2 function by RNAi or with a hypomorphic allele causes defects in AC 
invasion. Genetic analysis indicates that HLH-2 has functions outside of the 
FOS-1A pathway. Using expression analysis, we identify three genes that are 
transcriptionally regulated by HLH-2: the protocadherin cdh-3, and two genes 
encoding secreted extracellular matrix proteins, mig-6/papilin and 
him-4/hemicentin. Further, we show that reduction of HLH-2 function causes 
defects in polarization of F-actin to the invasive cell membrane, a process 
required for the AC to generate protrusions that breach the basement membrane. 
This work identifies HLH-2 as a regulator of the invasive phenotype in the AC, 
adding to our understanding of the transcriptional networks that control cell 
invasion.