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. 2019 Jan 9;11(1):63. doi: 10.3390/cancers11010063

Figure 7.

Figure 7

Model outlining the role of LDOC1 as a cigarette smoke-sensitive negative regulator of IL6/JAK2/STAT3 in lung cancer. LDOC1 functions as an adaptor between pJAK2 and E3 ligase LNX1. After cigarette smoke exposure, LDOC1 expression was downregulated or silenced by promoter hypermethylation, which led to inefficient ubiquitination of pJAK2 because a LNX1–pJAK2 complex could not form. Accumulated pJAK2 activated STAT3 through phosphorylation of STAT3Y706. pSTAT3Y706 translocated to the nucleus, where it regulated the expression of target genes such as IL-6. At an increased concentration, IL-6 bound to cell-surface receptor gp130, resulting in the phosphorylation of JAK. In this manner, LDOC1 knockdown drove lung cancer progression by reinforcing the IL6/JAK2/STAT3 signaling loop.