The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway

Abstract

Human BCL7 gene family consists of BCL7A, BCL7B, and BCL7C. A number of clinical studies have reported that BCL7 family is involved in cancer incidence, progression, and development. Among them, BCL7B, located on chromosome 7q11.23, is one of the deleted genes in patients with Williams-Beuren syndrome. Although several studies have suggested that malignant diseases occurring in patients with Williams-Beuren syndrome are associated with aberrations in BCL7B, little is known regarding the function of this gene at the cellular level. In this study, we focused on bcl-7, which is the only homolog of BCL7 gene family in Caenorhabditis elegans, and analyzed bcl-7 deletion mutants. As a result, we found that bcl-7 is required for the asymmetric differentiation of epithelial seam cells, which have self-renewal properties as stem cells and divide asymmetrically through the WNT pathway. Distal tip cell development, which is regulated by the WNT pathway in Caenorhabditis elegans, was also affected in bcl-7-knockout mutants. Interestingly, bcl-7 mutants exhibited nuclear enlargement, reminiscent of the anaplastic features of malignant cells. Furthermore, in KATOIII human gastric cancer cells, BCL7B knockdown induced nuclear enlargement, promoted the multinuclei phenotype and suppressed cell death. In addition, this study showed that BCL7B negatively regulates the Wnt-signaling pathway and positively regulates the apoptotic pathway. Taken together, our data indicate that BCL7B/BCL-7 has some roles in maintaining the structure of nuclei and is involved in the modulation of multiple pathways, including Wnt and apoptosis. This study may implicate a risk of malignancies with BCL7B-deficiency, such as Williams-Beuren syndrome.

Comprehensive Profiling of Lysine Acetylome in Baculovirus Infected Silkworm (Bombyx mori) Cells

“…Bcl7 gene family consists of Bcl7A, Bcl7B , and Bcl7C . Uehara T et al found that Bcl7 was required for normal seam cell development in Caenorhabditis elegans . Furthermore, Bcl7 knockdown suppressed KATOIII human gastric cancer cell death and regulated the Wnt‐signaling and apoptotic pathways .…”

“…Uehara T et al found that Bcl7 was required for normal seam cell development in Caenorhabditis elegans . Furthermore, Bcl7 knockdown suppressed KATOIII human gastric cancer cell death and regulated the Wnt‐signaling and apoptotic pathways . So, Bcl7A may play an important role in the development of BmN cells.…”

Twins with Williams-Beuren Syndrome and Discordance for Wilms Tumor

“…[1,12] BCL7B, another Wnt pathway tumor suppressor gene located on WBSCR, could also contribute to malignancy in patients with WBS. [13] Such genes, together with others involved in DNA repair (e.g., RFC2), could have a role in WT tumorogenesis. In this regard and due to inconclusive evidence of concordance for WT in twins, [14] we follow both twins regularly.…”

“…identified possible Wnt pathway target genes in WT tumorogenesis, including FZD9 , positioned on WBSCR . BCL7B, another Wnt pathway tumor suppressor gene located on WBSCR, could also contribute to malignancy in patients with WBS . Such genes, together with others involved in DNA repair (e.g., RFC2), could have a role in WT tumorogenesis.…”

Concomitant AID Expression and BCL7A Loss Associates With Accelerated Phase Progression and Imatinib Resistance in Chronic Myeloid Leukemia

“…BCL7A belongs to the BCL7 family, which includes BCL7B and BCL7C , and is a known pro-apoptotic tumor suppressor in B-cell oncogenesis. Specifically, BCL7B suppresses β-catenin expression, causing Wnt signaling inhibition [7]. Importantly, β-catenin deregulation in Wnt signaling is associated with genomic instability that can induce oncogenic translocations in T-cell lymphoma and AML [58].…”