在癌細胞中蛋白酪胺酸去磷酸酶SHP2促進invadopodia形成

The Protein Tyrosine Phosphatase SHP2 Promotes Invadopodia Formation in Cancer cells

蔡宛臻(Wan-Chen Tsai)

指導教授 ： 陳鴻震

國立中興大學/生命科學院/生命科學系所/碩士(2014年)

摘要

SHP2為非受體型蛋白酪胺酸去磷酸酶中的一員，其基因編碼為PTPN11。近年來報導指出SHP2在體內中會促進癌細胞轉移，但其機制還不了解。Invadopodia是由肌動蛋白所組成，突出於細胞腹側的actin特化結構，此結構具有瓦解細胞外基質及侵犯組織促進細胞移動的能力。SHP2促進腫瘤侵犯組織是否透過形成invadopodia還不清楚。我的研究發現，在多種癌細胞中，經由shRNA抑制SHP2的表現會降低invadopodia的形成，在頭頸部癌細胞SAS中最為顯著。更進一步發現，在另外一株頭頸部癌細胞CAL-27中過度表現SHP2會促進invadopodia形成和增加瓦解細胞外基質的能力。已知SHP2會抑制RhoA活性，在我的研究中證明抑制SHP2會促進RhoA活性，若給予RhoA特異性抑制劑肉毒梭菌C3胞外黴和ROCK抑制劑Y27632，發現會促進invadopodia形成。綜合以上結果得知，在頭頸部癌中SHP2促進invadopodia形成可能經由抑制Rho訊號。

關鍵字

酪胺酸去磷酸酶 ； 侵犯偽足

並列摘要

Src homology domain-containing phosphatase 2 (SHP2), a non-receptor protein tyrosine phosphatase, is encoded by PTPN11 gene. Recent studies indicate that SHP2 plays a role in promoting cancer metastasis in vivo, but the mechanism is poorly understood. Invadopodia are actin-enriched membrane protrusions important for extracellular matrix degradation and invasive cell motility. It remains unclear if SHP2 promotes tumor invasion through facilitating invadopodia formation. In this study, we found that knockdown of SHP2 suppressed invadopodia formation in several types of cancer cells, in particular, in head and neck squamous cell carcinomas SAS. In contrast, overexpression of FLAG tagged-SHP2 facilitated the invadopodia formation in head and neck squamous cell carcinomas CAL-27. SHP2 has been reported to suppress Rho activity. The suppression of invadopodia formation by SHP2 depletion was restored by the Clostridium botulinum C3 exoenzyme (a Rho GTPase inhibitor) and Y27632 (an inhibitor for Rho-associated kinase). Our results together suggest that SHP2 may promote invadopodia formation through inhibition of the Rho signaling in head and neck squamous cell carcinomas.

並列關鍵字

Phosphatase ； SHP2 ； Invadopodia ； RhoA

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