title: Hematopoietic PBX-Interaction Protein Promotes Breast Cancer Sensitivity to Paclitaxel Through a Microtubule-Dependent Mechanism.
abstract: OBJECTIVE
  Recently, microtubule-binding proteins (MBPs) have been implicated in modulation of paclitaxel sensitivity in many cancers, highlighting their potential as biomarkers predictive of treatment outcomes and as therapeutic targets that can be pharmacologically manipulated. This study is aimed to determine the impact of the MBP hematopoietic PBX-interaction protein (HPIP) on breast cancer cell sensitivity to paclitaxel.
  
  
  RESULTS
  In this study, we show that breast cancer cells (MCF-7 and MDA-MB-231) overexpressing HPIP were more sensitive to paclitaxel treatment as evaluated by MTT assay, exhibiting a significant reduction in IC50 of paclitaxel compared with the control. In transwell assay, breast cancer cells overexpressing HPIP, but not the cells transfected with empty vector, showed significant migration inhibition in response to paclitaxel. Furthermore, in vitro assays show that combined HPIP and paclitaxel enabled a more rapid and more complete microtubule assembly than paclitaxel alone, and accordingly HPIP plus paclitaxel-stabilized microtubule displayed slower dissociation dynamics upon dilution and cooling. Notably, overexpression of HPIP decreased the cellular level of HDAC6, leading to increased acetylation of tubulin as shown by Western blot and immunofluorescence imaging analysis.
  
  
  CONCLUSIONS
  Collectively, HPIP sensitized breast cancer cells to paclitaxel through a microtubule-dependent mechanism. Our finding hints at a clinical value of HPIP in breast cancer patient selection for paclitaxel-based regimens in the context of precision medicine.
authors.affiliation: 1 Tianjin Central Hospital of Gynecology Obstetrics , Tianjin, People's Republic of China .
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: 2 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine , Tianjin, People's Republic of China .
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Tian
authors.affiliation: 1 Tianjin Central Hospital of Gynecology Obstetrics , Tianjin, People's Republic of China .
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 1 Tianjin Central Hospital of Gynecology Obstetrics , Tianjin, People's Republic of China .
authors.forename: Rui
authors.initials: R
authors.lastname: Feng
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
chemical_list: C469750:HCFC1R1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D014404:Tubulin; D017239:Paclitaxel
keywords: breast cancer; hematopoietic PBX-interaction protein; paclitaxel