Abstract
PBX3 is a homeodomain-containing transcription factor of the pre-B cell leukemia (PBX) family, members of which have extensive roles in early development and some adult processes. A number of features distinguish PBX3 from other PBX proteins, including the ability to form specific and stable interactions with DNA in the absence of cofactors. PBX3 has frequently been reported as having a role in the development and maintenance of a malignant phenotype, and high levels of PBX3 tumor expression have been linked to shorter overall survival in cancer. In this review we consider the similarities and differences in the function of PBX3 in different cancer types and draw together the core signaling pathways involved to help provide a better insight into its potential as a therapeutic target.
Highlights
The pre-B cell leukemia (PBX) family is a group of homeodomain-containing transcription factors and homologues of the Drosophila Extradenticle gene [1]
Elevated PBX3 tumor expression has been found to be associated with a number of key clinical and pathological indicators associated with a poor outcome in gastric cancer, including invasion depth, and the stage and grad e of the tumor [47,48], and, correspondingly, tumor expression of miR-144-3p, which blocks PBX3 expression at the post-transcriptional level, is negatively correlated with tumor stage, invasion depth, and nodal metastasis [30]
Overexpression of PBX3 without its 3’UTR-let-7c-binding sequence was able to rescue cells from tumor suppressive effects of this miR [17]. These findings are in agreement with those of the study looking at PBX3 RNA expression in colorectal tumors, in which high expression levels were found to be significantly associated with lymph node invasion, metastasis, advanced pathological stage, and shorter overall survival [51]
Summary
The pre-B cell leukemia (PBX) family is a group of homeodomain-containing transcription factors and homologues of the Drosophila Extradenticle gene [1]. PBX proteins were initially and most extensively characterized for their role in early development, especially anteroposterior patterning of the main body axis and the limbs through forming heterodimers with HOX proteins, which are themselves expressed in a spatial order along this axis [3]. Many of these studies identify either PBX1 or PBX2 as HOX-binding partners, and PBX3 [4], which was characterized relatively late, has had very few specific developmental roles ascribed to it. We review the molecular mechanisms underlying these oncogenic functions in different cancers, and consider the potential of PBX3 as a therapeutic target
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