PBX1 as a novel master regulator in cancer: Its regulation, molecular biology, and therapeutic applications.

PBX1 is a critical transcription factor at the top of various cell fate-determining pathways. In cancer, PBX1 stands at the crossroads of multiple oncogenic signaling pathways and mediates responses by recruiting a broad repertoire of downstream targets. Research thus far has corroborated the involvement of PBX1 in cancer proliferation, resisting apoptosis, tumor-associated neoangiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, immune evasion, genome instability, and dysregulating cellular metabolism. Recently, our understanding of the functional regulation of the PBX1 protein has advanced, as increasing evidence has depicted a regulatory network consisting of transcriptional, post-transcriptional, and post-translational levels of control mechanisms. Furthermore, accumulating studies have supported the clinical utilization of PBX1 as a prognostic or therapeutic target in cancer. Preliminary results showed that PBX1 entails vast potential as a targetable master regulator in the treatment of cancer, particularly in those with high-risk features and resistance to other therapeutic strategies. In this review, we will explore the regulation, protein-protein interactions, molecular pathways, clinical application, and future challenges of PBX1.

• Publication year

  2024

• Venue

  Biochimica et biophysica acta. Reviews on cancer

• Publication date

  2024-02-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.bbcan.2024.189085PMID 38341110
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The advances of E2A-PBX1 fusion in B-cell acute lymphoblastic Leukaemia

  2023cited by this paper
• G-quadruplexes folding mediates downregulation of PBX1 expression in melanoma

  2023cited by this paper
• PBX1 Participates in Estrogen-Mediated Bladder Cancer Progression and Chemo-Resistance Affecting Estrogen Receptors.

  2022cited by this paper
• HOX and PBX gene dysregulation as a therapeutic target in glioblastoma multiforme

  2022cited by this paper
• Whole-exome sequencing and bioinformatics analysis of a case of non-alpha-fetoprotein-elevated lung hepatoid adenocarcinoma

  2022cited by this paper
• An insight into the diagnostic and prognostic value of HOX A13’s expression in non‐muscle invasive bladder cancer

  2022cited by this paper
• Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer

  2022cited by this paper
• Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma.

  2022cited by this paper
• The regulation of PBXs and their emerging role in cancer

  2022cited by this paper
• Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer

  2022cited by this paper
• m6A‐mediated regulation of PBX1‐GCH1 axis promotes gastric cancer proliferation and metastasis by elevating tetrahydrobiopterin levels

  2022cited by this paper
• CD46 protects the bladder cancer cells from cetuximab-mediated cytotoxicity

  2022cited by this paper
• Functional characterization of the PI3K/AKT/MTOR signaling pathway for targeted therapy in B-precursor acute lymphoblastic leukemia

  2022cited by this paper
• PBX1, EMCN and ERG are associated with the sub-clusters and the prognosis of VHL mutant clear cell renal cell carcinoma

  2022cited by this paper
• The TALE never ends: A comprehensive overview of the role of PBX1, a TALE transcription factor, in human developmental defects

  2022cited by this paper
• Identification of Tumor Suppressive Genes Regulated by miR-31-5p and miR-31-3p in Head and Neck Squamous Cell Carcinoma

  2021cited by this paper
• Genetic features of B‐cell lymphoblastic lymphoma with TCF3‐PBX1

  2021cited by this paper
• HPIP protooncogene differentially regulates metabolic adaptation and cell fate in breast cancer cells under glucose stress via AMPK and RNF2 dependent pathways.

  2021cited by this paper
• Poor prognosis of B‐cell acute lymphoblastic leukemia with TCF/PBX1 fusion gene and ovarian involvement at diagnosis: Two case reports and review of the literature

  2021cited by this paper
• PBX1: a key character of the hallmarks of cancer

  2021cited by this paper
• CPNE1 Enhances Colorectal Cancer Cell Growth, Glycolysis, and Drug Resistance Through Regulating the AKT-GLUT1/HK2 Pathway

  2021cited by this paper
• Mediator subunit MED1 is required for E2A-PBX1–mediated oncogenic transcription and leukemic cell growth

  2021cited by this paper
• Short-Form Thymic Stromal Lymphopoietin (sfTSLP) Is the Predominant Isoform Expressed by Gynaecologic Cancers and Promotes Tumour Growth

  2021cited by this paper
• Emerging role of pioneer transcription factors in targeted ERα positive breast cancer

  2021cited by this paper
• MicroRNA-141-3p inhibits the progression of oral squamous cell carcinoma via targeting PBX1 through the JAK2/STAT3 pathway

  2021cited by this paper
• MEIS1 in Hematopoiesis and Cancer. How MEIS1-PBX Interaction Can Be Used in Therapy

  2021cited by this paper
• Development of small molecule inhibitors targeting PBX1 transcription signaling as a novel cancer therapeutic strategy

  2021cited by this paper
• Clinical features and prognostic impact of TCF3-PBX1 in childhood acute lymphoblastic leukemia: A single-center retrospective study of 837 patients from China.

  2021cited by this paper
• A Computer-Based Methodology to Design Non-Standard Peptides Potentially Able to Prevent HOX-PBX1-Associated Cancer Diseases

  2021cited by this paper
• Noncoding RNA therapeutics — challenges and potential solutions

  2021cited by this paper
• PBX1-directed stem cell transcriptional program drives tumor progression in myeloproliferative neoplasm

  2021cited by this paper
• rs6426881 in the 3'-UTR of PBX1 is involved in breast and gastric cancers via altering the binding potential of miR-522-3p

  2021cited by this paper
• A novel c-Kit/phospho-prohibitin axis enhances ovarian cancer stemness and chemoresistance via Notch3—PBX1 and β-catenin—ABCG2 signaling

  2020cited by this paper
• Mapping the native interaction surfaces of PREP1 with PBX1 by cross-linking mass-spectrometry and mutagenesis

  2020cited by this paper
• Upregulation of S100A10 in metastasized breast cancer stem cells

  2020cited by this paper
• Master regulator genes and their impact on major diseases

  2020cited by this paper
• Cytogenetic abnormalities in multiple myeloma: association with disease characteristics and treatment response

  2020cited by this paper
• Upregulation of microRNA-650 by PBX1 is correlated with the development of Helicobacter pylori-associated gastric carcinoma.

  2020cited by this paper
• Ibrutinib is not an effective drug in primografts of TCF3-PBX1

  2020cited by this paper
• HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours

  2020cited by this paper
• FABP5 promotes lymph node metastasis in cervical cancer by reprogramming fatty acid metabolism

  2020cited by this paper
• Modulating transcription factor activity: Interfering with protein-protein interaction networks.

  2020cited by this paper
• PBX1 is a valuable prognostic biomarker for patients with breast cancer

  2020cited by this paper
• RGMB-AS1/miR-4428/PBX1 axis drives the progression of cervical cancer

  2020cited by this paper
• PBX1 Increases the Radiosensitivity of Oesophageal Squamous Cancer by Targeting of STAT3

  2020cited by this paper
• Oncogenic heterogeneous nuclear ribonucleoprotein D-like modulates the growth and imatinib response of human chronic myeloid leukemia CD34+ cells via pre-B-cell leukemia homeobox 1

  2019cited by this paper
• FZD2 regulates cell proliferation and invasion in tongue squamous cell carcinoma

  2019cited by this paper
• Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy.

  2019cited by this paper
• Comparative Analysis of Putative Prognostic and Predictive Markers in Neuroblastomas: High Expression of PBX1 Is Associated With a Poor Response to Induction Therapy

  2019cited by this paper
• NANOG Attenuates Hair Follicle-Derived Mesenchymal Stem Cell Senescence by Upregulating PBX1 and Activating AKT Signaling

  2019cited by this paper
• Inhibition of the deubiquitinase USP9x induces pre-B cell homeobox 1 (PBX1) degradation and thereby stimulates prostate cancer cell apoptosis

  2019cited by this paper
• Targeting HOX/PBX dimer formation as a potential therapeutic option in esophageal squamous cell carcinoma

  2019cited by this paper
• The human HOXA9 protein uses paralog-specific residues of the homeodomain to interact with TALE-class cofactors

  2019cited by this paper
• JOSD1 inhibits mitochondrial apoptotic signalling to drive acquired chemoresistance in gynaecological cancer by stabilizing MCL1

  2019cited by this paper
• Prediction of neuroblastoma cell response to treatment with natural or synthetic retinoids using selected protein biomarkers

  2019cited by this paper
• BolA family member 2 enhances cell proliferation and predicts a poor prognosis in hepatocellular carcinoma with tumor hemorrhage

  2019cited by this paper
• Advances and Challenges in Studying Noncoding RNA Regulation of Drug Metabolism and Development of RNA Therapeutics.

  2019cited by this paper
• LncRNA-uc.40 silence promotes P19 embryonic cells differentiation to cardiomyocyte via the PBX1 gene

  2018cited by this paper
• Inhibition of cell proliferation and migration in non‑small cell lung cancer cells through the suppression of LYPLA1.

  2018cited by this paper
• Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer.

  2018cited by this paper
• SETDB2 Links E2A-PBX1 to Cell-Cycle Dysregulation in Acute Leukemia through CDKN2C Repression

  2018cited by this paper
• Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases

  2018cited by this paper
• PBX1 promotes the cell proliferation via JAK2/STAT3 signaling in clear cell renal carcinoma.

  2018cited by this paper
• Post-transcriptional regulation of gene expression and human disease.

  2018cited by this paper
• Prep1, A Homeodomain Transcription Factor Involved in Glucose and Lipid Metabolism

  2018cited by this paper
• Targeting HOX-PBX interactions causes death in oral potentially malignant and squamous carcinoma cells but not normal oral keratinocytes

  2018cited by this paper
• FoxC1 promotes epithelial-mesenchymal transition through PBX1 dependent transactivation of ZEB2 in esophageal cancer.

  2017cited by this paper
• PBX1 as Pioneer Factor: A Case Still Open

  2017cited by this paper
• uc.38 induces breast cancer cell apoptosis via PBX1.

  2017cited by this paper
• A tale of TALE, PREP1, PBX1, and MEIS1: Interconnections and competition in cancer.

  2017cited by this paper
• Drugging the 'undruggable' cancer targets

  2017cited by this paper
• Targeting HOX/PBX dimers in cancer

  2017cited by this paper
• A hydrophobic residue in the TALE homeodomain of PBX1 promotes epithelial-to-mesenchymal transition of gastric carcinoma

  2017cited by this paper
• SERP1 is a novel marker of poor prognosis in pancreatic ductal adenocarcinoma patients via anti-apoptosis and regulating SRPRB/NF-κB axis

  2017cited by this paper
• Overexpression of lipid metabolism genes and PBX1 in the contralateral breasts of women with estrogen receptor‐negative breast cancer

  2017cited by this paper
• Inhibition of HOX/PBX dimer formation leads to necroptosis in acute myeloid leukemia cells

  2017cited by this paper
• The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia

  2016cited by this paper
• Ovarian Cancer Chemoresistance Relies on the Stem Cell Reprogramming Factor PBX1.

  2016cited by this paper
• The Ring Finger Protein RNF6 Induces Leukemia Cell Proliferation as a Direct Target of Pre-B-cell Leukemia Homeobox 1*

  2016cited by this paper
• Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer

  2016cited by this paper
• HOX transcription factors are potential targets and markers in malignant mesothelioma

  2016cited by this paper
• The prognostic significance of specific HOX gene expression patterns in ovarian cancer

  2016cited by this paper
• Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia

  2016cited by this paper
• Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature

  2016cited by this paper
• To Be Specific or Not: The Critical Relationship Between Hox And TALE Proteins.

  2016cited by this paper
• The central nervous system microenvironment influences the leukemia transcriptome and enhances leukemia chemo-resistance

  2016cited by this paper
• Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia.

  2015cited by this paper
• Idelalisib: First-in-Class PI3K Delta Inhibitor for the Treatment of Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, and Follicular Lymphoma

  2015cited by this paper
• Arginine methylation of hnRNPUL1 regulates interaction with NBS1 and recruitment to sites of DNA damage

  2015cited by this paper
• The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

  2015cited by this paper
• Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia.

  2015cited by this paper
• Direct and Indirect Targets of the E2A-PBX1 Leukemia-Specific Fusion Protein

  2014cited by this paper
• Inhibition of non-small-cell lung cancer cell proliferation by Pbx1.

  2014cited by this paper
• Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-β–SMAD3 pathway in non-small cell lung adenocarcinoma

  2014cited by this paper
• Targeting HOX transcription factors in prostate cancer

  2014cited by this paper
• Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and tumorigenesis

  2014cited by this paper
• PBX1 Is a Favorable Prognostic Biomarker as It Modulates 13-cis Retinoic Acid–Mediated Differentiation in Neuroblastoma

  2014cited by this paper
• A low level of GPR37 is associated with human hepatocellular carcinoma progression and poor patient survival.

  2014cited by this paper
• GCN5 acetylates and regulates the stability of the oncoprotein E2A-PBX1 in acute lymphoblastic leukemia

  2013cited by this paper
• Rational design of an immunoconjugate for selective knock-down of leukemia-specific E2A-PBX1 fusion gene expression in human Pre-B leukemia.

  2013cited by this paper

• TAT-PBX1 Reverses Hyperglycemia Through β-Cell Regeneration and Functional Restoration in an STZ-Induced Diabetic Model

  2026cites this paper
• PBX1-mediated transcription of AP1M2 promotes triple-negative breast cancer malignant progression and docetaxel resistance.

  2026cites this paper
• BHLHE40 Is a Transcriptional Regulatory Target of NFE2L3 in Triple-Negative Breast Cancer

  2026cites this paper
• Lactate programs PBX1 lactylation and mesangial proliferation in lupus nephritis

  2025cites this paper
• Expression of G-quadruplex coordinates BRCA1, CDH1, and RASSF1 via DNA methylation in mouse breast cancer cells.

  2025cites this paper
• A Brief Review on the Role of the Transcription Factor PBX1 in Hematologic Malignancies

  2025influential citation
• A rare PBX1 variant identified in adulthood: a case report

  2025cites this paper
• PBX1 promotes osteoporosis by upregulating HMGB1 to suppress osteogenic differentiation of bone marrow mesenchymal stem cells

  2025cites this paper
• Transcriptomic insights into GSDME-driven pyroptosis in head and neck cancer

  2025cites this paper
• miR-196-5p regulates myogenesis and induces slow-switch fibers formation by targeting PBX1.

  2025cites this paper
• Inhibition of the FEN1-PBX1 axis elicits cellular senescence in breast cancer via the increased intracellular reactive oxygen species levels

  2025cites this paper
• MAPPING CHANGES OF MIRNA-MRNA NETWORKS IN LEISHMANIA-INFECTED MACROPHAGES PREDICTS REGULATORY MIRNA-TF LOOPS AS NOVEL TARGETS OF PARASITE IMMUNE SUBVERSION

  2025cites this paper
• Transcription factors and hormone receptors: Sex‑specific targets for cancer therapy (Review)

  2024cites this paper
• Metabolic Switch in Endocrine Resistant Estrogen Receptor Positive Breast Cancer

  2024cites this paper
• UBE2T promotes stage I lung adenocarcinoma progression through PBX1 ubiquitination and PBX1/RORA regulation

  2024cites this paper
• Comprehensive summary: the role of PBX1 in development and cancers

  2024cites this paper
• Thyrotoxic Effects of Mixed Exposure to Perfluorinated Compounds: Integrating Population-Based, Toxicogenomic, Animal, and Cellular Evidence to Elucidate Molecular Mechanisms and Identify Potential Effector Targets.

  2024cites this paper