[Functional properties of the WNT11 new isoform, expressed in colon carcinoma cell line HT29].
Colon carcinoma is a common type of neoplastic transformation. Mechanisms of its establishment and progression have been studying for several decades. Aberrant activation of the canonical Wnt signaling is frequently observed in colon carcinoma cells. Moreover, expression of the "noncanonical" Wnt ligands is also detected in this type of cancer. However, the implication of the noncanonical Wnt signaling in carcinogenesis and colorectal cancer (CRC) progression is still unclear. Here, to elucidate the characteristic features of the noncanonical Wnt signaling activation in CRC the expression of the "noncanonical" ligand hWnt11 has been studied. It was shown for the first time that expression of the hWnt11 in CRC is accompanied by the alternative splicing. The new hWnt11 isoform (hWnt11sp3) has been identified. Unlike to hWnt11, this isoform is not secreted and lacks the ability to inhibit the canonical Wnt signaling. Considering the canonical Wnt signaling inhibiting activity of hWnt11, different functional properties of the ligand and its isoform may reflect a special role of the alternative splicing in carcinogenesis and tumor progression. Thus, due to the difference in their functional properties an existence of several Wnt isoforms should be taken into account for the investigation of the role of Wnt ligands.
A V
AV
Posviatenko
K V
KV
Kulikova
N V
NV
Gnuchev
G P
GP
Georgiev
A V
AV
Kibardin
S S
SS
Larin
D017398:Alternative Splicing / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008024:Ligands; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics
D008024:Ligands; D020033:Protein Isoforms; D051153:Wnt Proteins; C540523:Wnt11 protein, human