Cancer as an Embryological Phenomenon and Its Developmental Pathways: A Hypothesis regarding the Contribution of the Noncanonical Wnt Pathway

Figure 3

Regulatory loop among Kaiso, Wnt11/5a and Suz12. (a) The genes Wnt11 and Wnt5a upregulate Suz12 expression (suppressor of zeste 12) acting in the nucleus as transcriptional factors. Kaiso and TCF/LEF cooperate to repress the transcription of Wnt11 and Suz12 activate the transcription of Kaiso. This regulatory loop proposed could be reinforced by other nonclassical-Pc-functions as, for example: (i) EZH2 physically interacts directly with β-catenin, functionally improves the Wnt target gene expression and phenotypically leads to the overexpression of c-Myc and cyclin D1 [54, 55], (ii) BMI1 might also act as an activator of WNT pathway by repressing Dickkopf (DKK), and its negative regulation results in upregulation of c-Myc that participate in a positive feedback loop, activating the transcription of BMI1 [56], and (iii) the overexpression of WNT/β-catenin signaling can also lead to increase Wnt11 expression [58–60]. (b) Expression analysis of Kaiso in Suz12 knockdown cells. K562 cells were transfected with siRNA-Suz12 (25nM). Twenty-four hours later, RNA was isolated and subjected to Real Time RT-PCR to quantify expression of Kaiso after normalization to β-actin and compared to the scrambled knockdown cells. Data were expressed as mean ± standard deviation (SD). Columns, mean (n = 3); error bars, SD; p < 0.001.

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