Globally, the idea that protein secretion-transcription loops operate to determine metastatic proclivities in primary tumor cells is also suggested by the finding that TMED9, CNIH4, as well as TGFA [73], harbor high-confidence consensus GLI-binding sites within 5 Kb upstream of the transcriptional start site, whereas TMED3 harbors TCF-binding sites instead (Supplemental Fig. 14). This evidence concerns the gene HNF4A and neoplasm.