title: Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma.
abstract: BACKGROUND
  Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC.
  
  
  METHODS
  To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients.
  
  
  RESULTS
  Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients.
  
  
  CONCLUSIONS
  In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.
authors.affiliation: Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre (ACTREC), Kharghar, Navi Mumbai, India.
authors.forename: Hunain
authors.initials: H
authors.lastname: Alam
authors.forename: Amruta V
authors.initials: AV
authors.lastname: Bhate
authors.forename: Prakash
authors.initials: P
authors.lastname: Gangadaran
authors.forename: Sharda S
authors.initials: SS
authors.lastname: Sawant
authors.forename: Shimul
authors.initials: S
authors.lastname: Salot
authors.forename: Lalit
authors.initials: L
authors.lastname: Sehgal
authors.forename: Prerana P
authors.initials: PP
authors.lastname: Dange
authors.forename: Devendra A
authors.initials: DA
authors.lastname: Chaukar
authors.forename: Anil K
authors.initials: AK
authors.lastname: D'cruz
authors.forename: Sadhna
authors.initials: S
authors.lastname: Kannanl
authors.forename: Rajiv
authors.initials: R
authors.lastname: Gude
authors.forename: Shubhada
authors.initials: S
authors.lastname: Kane
authors.forename: Sorab N
authors.initials: SN
authors.lastname: Dalal
authors.forename: Milind M
authors.initials: MM
authors.lastname: Vaidya
mesh_terms: D000199:Actins / Q000648:ultrastructure; D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000648:ultrastructure; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008840:Microfilament Proteins / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000502:physiology
chemical_list: D000199:Actins; D002352:Carrier Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C020324:fascin; D020778:Matrix Metalloproteinase 2