Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma

BMC Cancer

Hunain Alam²  Amruta V Bhate²  Prakash Gangadaran²  Sharda S Sawant²  Shimul Salot²  Lalit Sehgal²  Prerana P Dange²  Devendra A Chaukar³  Anil K D'cruz³  Sadhna Kannanl²  Rajiv Gude²  Shubhada Kane¹  Sorab N Dalal²  Milind M Vaidya² 

[1] Dept. of Pathology, Tata Memorial Hospital, Parel, Mumbai, India-400012

[2] Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre (ACTREC), Kharghar, Navi Mumbai, India-410210

[3] Oral Surgery, Head and Neck Unit, Tata Memorial Hospital, Parel, Mumbai, India-400012

关键词: OSCC;    Metastasis;    Invasion;    Cell migration;    Fascin;   

Others  :  1080575
DOI  :  10.1186/1471-2407-12-32

 received in 2011-10-06, accepted in 2012-01-20,  发布年份 2012

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2012 Alam et al; licensee BioMed Central Ltd.

【 图 表 】

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