CCN2 and neoplasm: Accordingly, levels of downstream molecules CTGF, PAI-1, and Snail were significantly up-regulated in ESCC tissues with high levels of P. gingivalis. Unexpectedly, downstream target genes of TGFβ signaling involving cell-cycle suppression and apoptosis promotion were up-regulated in response to P. gingivalis. These TGFβ-responding cells may represent highly aggressive tumor-initiating stem cells of SCC [34].