Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma.
Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma.
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DOI：
10.1186/1471-2407-12-32
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发表时间：
2012-01-20
期刊：
影响因子：
3.8
通讯作者：
Vaidya MM
中科院分区：
文献类型：
--
作者：
Alam H;Bhate AV;Gangadaran P;Sawant SS;Salot S;Sehgal L;Dange PP;Chaukar DA;D'cruz AK;Kannanl S;Gude R;Kane S;Dalal SN;Vaidya MM
Fascin 是一种球状肌动蛋白交联蛋白，在细胞突起中形成平行肌动蛋白束方面发挥着重要作用，并被发现与包括口腔鳞状细胞癌 (OSCC) 在内的多种类型癌症中的肿瘤细胞侵袭和转移有关。此前，我们已经证明肌成束蛋白调节肌动蛋白聚合，从而促进 K8 耗尽的 OSCC 细胞的细胞运动。在本研究中，我们研究了肌成束蛋白在 OSCC 肿瘤进展中的作用。为了了解肌成束蛋白在 OSCC 发生和/或进展中的作用，在 OSCC 衍生细胞 AW13516 中过度表达肌成束蛋白以及载体控制。使用伤口愈合、博伊登室、细胞粘附、悬滴、软琼脂和致瘤性测定来研究表型。此外，使用免疫组织化学检查了人 OSCC 样本 (N = 131) 中肌成束蛋白的表达，其表达水平与患者的临床病理参数相关。 OSCC 衍生细胞中肌成束蛋白过度表达导致细胞迁移、细胞侵袭和 MMP-2 活性显着增加。此外，这些细胞的磷酸化 AKT、ERK1/2 和 JNK1/2 水平增加。我们的体外结果与肌成束蛋白表达与 OSCC 患者临床病理参数的相关研究一致。 OSCC中Fascin的表达与患者的肿瘤分期增加（P = 0.041）、淋巴结转移增加（P = 0.001）、分化程度降低（P = 0.005）、复发增加（P = 0.038）和生存期缩短（P = 0.004）具有统计学显着相关性。总之，我们的结果表明肌成束蛋白促进肿瘤进展并激活 OSCC 衍生细胞中的 AKT 和 MAPK 通路。此外，我们对 OSCC 中肌成束蛋白表达与患者临床病理参数的相关研究表明，肌成束蛋白可能有助于 OSCC 的预后和治疗。
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. 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. 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. 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.
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