However, TP53R172H may also increase JAK2/STAT3 signaling independent of gp130 cytokines through direct interaction with the gp130-associated phosphatase SHP2,17 reminiscent of the direct binding of the TP53R248Q protein to activated pSTAT3, thereby “short circuiting” the ligand dependency of the STAT3 signaling cascade during colon cancer progression.18 This evidence concerns the gene IL6ST and malignant colon neoplasm.