CBX7 is a tumor suppressor in mice and humans

Abstract

The CBX7 gene encodes a polycomb group protein that is known to be downregulated in many types of human cancers, although the role of this protein in carcinogenesis remains unclear. To shed light on this issue, we generated mice null for Cbx7. Mouse embryonic fibroblasts derived from these mice had a higher growth rate and reduced susceptibility to senescence compared with their WT counterparts. This was associated with upregulated expression of multiple cell cycle components, including cyclin E, which is known to play a key role in lung carcinogenesis in humans. Adult Cbx7-KO mice developed liver and lung adenomas and carcinomas. In in vivo and in vitro experiments, we demonstrated that CBX7 bound to the CCNE1 promoter in a complex that included HDAC2 and negatively regulated CCNE1 expression. Finally, we found that the lack of CBX7 protein expression in human lung carcinomas correlated with CCNE1 overexpression. These data suggest that CBX7 is a tumor suppressor and that its loss plays a key role in the pathogenesis of cancer.

Mitogen-activated Protein Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7

“…This suggests that the Thr-118 phosphorylation motif holds important function and will be interesting to examine further in the context of cancer, particularly those tumors driven by ERK signaling, such as melanoma. To date, CBX7 has been implicated as an oncogene in prostate cancer and lymphoma, as well as a tumor suppressor in lung and breast cancer (17,18,58,59). Consistent with this, we noted a loss of Cbx7 expression (and T118ph) in a series of mouse mammary carcinoma cells with increasing metastatic ability.…”

Polycomb Genes are Associated with Response to Imatinib in Chronic Myeloid Leukemia

“…Both CBX6 and CBX7 have been suggested to play an oncosuppressive role in solid tumors [24] and, as shown in the Oncomine database, in myeloid leukemias (Figure 3). Notably, CBX7 oncosuppressive activity is predominant in hematologic neoplasms [25]. Taken together, this evidence suggests that CBX6 and CBX7 could play a tumor suppressive role in CML also, and that their concurrent activation upon imatinib treatment might lead to the silencing of prosurvival genes, thereby inducing neoplastic cell death and better short-term responses to imatinib.…”

CBX7 inhibits breast tumorigenicity through DKK‐1‐mediated suppression of the Wnt/β‐catenin pathway

“…CBX7, as a reader protein, plays an important role in promoting the recruitment of polycomb repressive complex (PRC)-1 to the target chromatin by recognizing PRC-2-mediated H3K27me3 (2). Moreover, CBX7 regulates gene expression by altering histone acetylation and DNA methylation (3)(4)(5)(6). Recent studies have suggested that CBX7 regulates the balance between self-renewal and differentiation in embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs) (7)(8)(9).…”