PBX1: a key character of the hallmarks of cancer.

Pre-B-cell leukemia homeobox transcription factor 1 (PBX1) was first identified as part of a fusion protein resulting from the chromosomal translocation t(1;19) in pre-B cell acute lymphoblastic leukemias. Since then, PBX1 has been associated with important developmental programs, and its expression dysregulation has been related to multifactorial disorders, including cancer. As PBX1 overexpression in many cancers is correlated to poor prognosis, we sought to understand how this transcription factor contributes to carcinogenesis, and to organize PBX1's roles in the hallmarks of cancer. There is enough evidence to associate PBX1 with at least five hallmarks: sustaining proliferative signaling, activating invasion and metastasis, inducing angiogenesis, resisting cell death, and deregulating cellular energetics. The lack of studies investigating a possible role for PBX1 on the remaining hallmarks made it impossible to defend or refute its contribution on them. However, the functions of some of the PBX1's transcription targets indicate a potential engagement of PBX1 in the avoidance of immune destruction and in the tumor-promoting inflammation hallmarks. Interestingly, PBX1 might be a player in tumor suppression by activating the transcription of some DNA damage response genes. This is the first review organizing PBX1 roles into the hallmarks of cancer. Thus, we encourage future studies to uncover the PBX1's underlying mechanisms to promote carcinogenesis, for it is a promising diagnostic and prognostic biomarker, as well as a potential target in cancer treatment.

T cells expressing the lupus susceptibility allele Pbx1d enhance autoimmunity and atherosclerosis in dyslipidemic mice.

Patients with systemic lupus erythematosus (SLE) present a high incidence of atherosclerosis, which contributes significantly to morbidity and mortality in this autoimmune disease. An impaired balance between regulatory (Treg) and follicular helper (Tfh) CD4+ T cells is shared by both diseases. However, whether there are common mechanisms of CD4+ T cell dysregulation between SLE and atherosclerosis remains unclear. Pre-B cell leukemia transcription factor 1 isoform d (Pbx1d) is a lupus susceptibility gene that regulates Tfh cell expansion and Treg cell homeostasis. Here, we investigated the role of T cells overexpressing Pbx1d in low-density lipoprotein receptor-deficient (Ldlr-/-) mice fed with a high-fat diet, an experimental model for atherosclerosis. Pbx1d-transgenic T cells exacerbated some phenotypes of atherosclerosis, which were associated with higher autoantibody production, increased Tfh cell frequency, and impaired Treg cell regulation, in Ldlr-/- mice as compared with control T cells. In addition, we showed that dyslipidemia and Pbx1d-transgenic expression independently impaired the differentiation and function of Treg cells in vitro, suggesting a gene/environment additive effect. Thus, our results suggest that the combination of Pbx1d expression in T cells and dyslipidemia exacerbates both atherosclerosis and autoimmunity, at least in part through a dysregulation of Treg cell homeostasis.