Disease relevance of WNT11

• Among various types of human primary tumors, WNT11 mRNA was up-regulated in four cases of colorectal adenocarcinoma, and a case of renal cell carcinoma [1].
• WNT11 mRNA was significantly up-regulated in a gastric cancer cell line MKN45 and a cervical cancer cell line SKG-IIIa [1].
• We found that WNT11 expression is elevated in hormone-independent prostate cancer cell lines [2].

High impact information on WNT11

• Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane [3].
• It is known that Wnt11 functionally interacts with several signaling components, the homologues of which control planar cell polarity in Drosophila melanogaster [3].
• We propose that Wnt11, by interacting with Frizzled 7 and Flamingo, modulates local cell contact persistence to coordinate cell movements during gastrulation [3].
• In the full-grown oocyte, before maturation, we find that axin levels are also regulated by Wnt11 and LRP6 [4].
• Regulation of ectodermal Wnt6 expression by the neural tube is transduced by dermomyotomal Wnt11: a mechanism of dermomyotomal lip sustainment [5].

Biological context of WNT11

• Up-regulation of WNT11 mRNA might play an important role in human carcinogenesis through activation of the WNT signaling pathway [1].
• The Ala121-Gly156-Ser271 WNT11 allele isolated in this study was also identified in human genome draft sequence AC069055 [1].
• Here, we cloned and characterized human WNT11, which showed three amino-acid substitutions (Ala121Thr, Gly156Arg, and Ser271Trp) compared with human WNT11 cDNA previously isolated by another group [1].
• Our observations are consistent with a model in which androgen depletion activates WNT11-dependent signals that inhibit androgen-dependent but not androgen-independent cell growth [2].
• Analysis of Wnt gene expression in prostate cancer: mutual inhibition by WNT11 and the androgen receptor [2].

Anatomical context of WNT11

• These have shown that the expression of human WNT11 is restricted to the perichondrium of the developing skeleton, lung mesenchyme, the tips of the ureteric buds and other areas of the urogenital system and the cortex of the adrenal gland [6].
• The 4.3-kb WNT11 mRNA was expressed in fetal lung, kidney, adult heart, liver, skeletal muscle, and pancreas [1].
• Xenopus Wnt11-R is expressed in neural tissue, dorsal mesenchyme derived from the dermatome region of the somites, the brachial arches, and the muscle layer of the heart, similar to the expression patterns reported for mouse and chicken Wnt11 [7].
• We show that Wnt1 and Wnt3a signaling from the neural tube inhibit Wnt6 expression in the medial surface ectoderm via dermomyotomal Wnt11 [5].
• Opposing roles of WNT-5A and WNT-11 in interleukin-1beta regulation of type II collagen expression in articular chondrocytes [8].

Associations of WNT11 with chemical compounds

• Growth of hormone-dependent LNCaP cells in hormone-depleted media led to increased WNT11 expression, which was repressed by the synthetic androgen R1881 [2].
• This repression was inhibited by the antiandrogen bicalutamide, suggesting that androgens negatively regulate WNT11 expression through the androgen receptor [2].

Regulatory relationships of WNT11

• WNT11 inhibited activation of the canonical Wnt pathway by WNT3A in HEK 293 cells and inhibited basal beta-catenin/Tcf transcriptional activity in LNCaP cells [2].
• Expression of WNT11 inhibited androgen receptor transcriptional activity and cell growth in androgen-dependent cells but not in androgen-independent cells [2].

Other interactions of WNT11

• However, expression of stabilized beta-catenin did not prevent the inhibition of androgen receptor transcriptional activity by WNT11 [2].
• Facial cell soma migration defects were associated with the coordinate downregulation of multiple components of the planar cell polarity pathway including Fzd7, Wnt11, Prickle1, Vang1 and Vang2 [9].
• Using truncated Frizzled and dominant-negative Wnt constructs, we then show the requirement of at least two Wnt proteins, Wnt8 and Wnt11, for Gli2/3-induced posterior mesodermal development [10].
• We found that Wnt5b and Wnt11 are restricted within the prehypertrophic chondrocytes of the cartilage elements, Wnt5a is found in the joints and perichondrium, while Wnt4 is expressed in the developing joints and, in some bones, a subset of the hypertrophic chondrocytes [11].

Analytical, diagnostic and therapeutic context of WNT11

• Molecular cloning and characterization of human WNT11 [1].
• Additional analysis indicated that WNT11 expression is also elevated in high-grade prostatic tumors and in hormone-independent xenografts [2].
• Supplementation of co-cultures with Wnt11-conditioned medium significantly enhanced the differentiation of CPCs to cardiomyocytes (1.7+/-0.3-fold), whereas Wnt3A-conditioned medium showed no effect [12].
• Moreover, in situ hybridization reveals expression, although not temporal coincidence of, Wnt11 and Wnt7a in specialized tissues in the developing heart in vivo [13].

References