In the integrin signaling networks of the HNSCC transcriptome, we identified several repressed inter-modular hubs: ACTN2, CAPN3 and TTN in Pre and TvN; and ILK, RHO-G and VCL in Meta. GRB2, ITGA5, ITGB6, ITGB7 and MAPK8 were distinguished as topologically significant hubs in the TvN interacting networks. Here, RHOG is linked to head and neck squamous cell carcinoma.