title: Fascin is involved in the chemotherapeutic resistance of breast cancer cells predominantly via the PI3K/Akt pathway.
abstract: BACKGROUND
  A major therapeutic challenge for breast cancer is the ability of cancer cells to evade killing of conventional chemotherapeutic agents. We have recently reported the actin-bundling protein (fascin) as a major regulator of breast cancer metastasis and survival.
  
  
  METHODS
  Survival of breast cancer patients that received chemotherapy and xenograft tumour model was used to assess the effect of chemotherapy on fascin-positive and -negative breast cancer cells. Molecular and cellular assays were used to gain in-depth understanding of the relationship between fascin and chemoresistance.
  
  
  RESULTS
  We showed a significant correlation between fascin expression and shorter survival in breast cancer patients who received chemotherapy. In xenograft experiments, fascin-positive cancer cells displayed significantly more resistance to chemotherapy-mediated apoptotic cell death than fascin-negative counterparts. This increased chemoresistance was at least partially mediated through PI3K/Akt signalling, and was paralleled by increased FAK phosphorylation, enhanced expression of the inhibitor of apoptosis proteins (XIAP and Livin) and suppression of the proapoptotic markers (caspase 9, caspase 3 and PARP).
  
  
  CONCLUSIONS
  This is the first report to demonstrate fascin involvement in breast cancer chemotherapeutic resistance, supporting the development of fascin-targeting drugs for better treatment of chemoresistance breast cancer.
authors.affiliation: Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: H
authors.initials: H
authors.lastname: Ghebeh
authors.affiliation: The Joint Center for Genomics Research, King Abdulaziz City for Sciences and Technology, Riyadh, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Al-Khaldi
authors.affiliation: Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: S
authors.initials: S
authors.lastname: Olabi
authors.affiliation: Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Al-Dhfyan
authors.affiliation: Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: F
authors.initials: F
authors.lastname: Al-Mohanna
authors.affiliation: Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: R
authors.initials: R
authors.lastname: Barnawi
authors.affiliation: Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Tulbah
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: T
authors.initials: T
authors.lastname: Al-Tweigeri
authors.affiliation: Department of Oncology, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: D
authors.initials: D
authors.lastname: Ajarim
authors.affiliation: Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, MBC: 03-99, P.O. Box: 3354, Riyadh 11211, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Al-Alwan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002352:Carrier Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D008840:Microfilament Proteins; C020324:fascin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt