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The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway


BCL7B, a member of the human BCL7 gene family, is deleted in patients with Williams-Beuren syndrome. Although several clinical studies have suggested that malignant diseases occurring in patients with Williams-Beuren syndrome are associated with aberrations in BCL7B, little is known regarding the physiological function of this gene. Here, we show that bcl-7, the only homolog of BCL7 gene family in Caenorhabditis elegans, regulates asymmetric cell differentiation in somatic “stem-like” seam cells through at least the Wnt pathway and promotes the apoptotic pathway. In addition, bcl-7 deletion mutants show enlarged nuclei in epidermis and germ cells. Furthermore, in KATOIII human gastric cancer cells, BCL7B knockdown induces nuclear enlargement, as observed in Caenorhabditis elegans, and promotes the multinucleated phenotype, both of which are reminiscent of malignant diseases. BCL7B also negatively regulates the Wnt-signaling pathway and positively regulates the apoptotic pathway, similar to Caenorhabditis elegans. Altogether, this study may open the door for understanding the function of BCL7 family in cell differentiation and malignancies.


Vyšlo v časopise: The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004921
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004921

Souhrn

BCL7B, a member of the human BCL7 gene family, is deleted in patients with Williams-Beuren syndrome. Although several clinical studies have suggested that malignant diseases occurring in patients with Williams-Beuren syndrome are associated with aberrations in BCL7B, little is known regarding the physiological function of this gene. Here, we show that bcl-7, the only homolog of BCL7 gene family in Caenorhabditis elegans, regulates asymmetric cell differentiation in somatic “stem-like” seam cells through at least the Wnt pathway and promotes the apoptotic pathway. In addition, bcl-7 deletion mutants show enlarged nuclei in epidermis and germ cells. Furthermore, in KATOIII human gastric cancer cells, BCL7B knockdown induces nuclear enlargement, as observed in Caenorhabditis elegans, and promotes the multinucleated phenotype, both of which are reminiscent of malignant diseases. BCL7B also negatively regulates the Wnt-signaling pathway and positively regulates the apoptotic pathway, similar to Caenorhabditis elegans. Altogether, this study may open the door for understanding the function of BCL7 family in cell differentiation and malignancies.


Zdroje

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