FHOD1 formin is upregulated in melanomas and modifies proliferation and tumor growth

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• 作者：Minna Peippo^a ; ^b ; ¹ ; ^{minna.peippo@utu.fi} ; Maria Gardberg^a ; ¹ ; ^{maria.gardberg@utu.fi} ; Tarja Lamminen^a ; ^b ; ^{tarja.lamminen@utu.fi} ; Katja Kaipio^a ; ^b ; ^{katja.kaipio@utu.fi} ; Olli Carpé ; n^a ; ^c ; ^{olli.carpen@utu.fi} ; Vanina D. Heuser^a ; ^b ; ^{vanina.heuser@utu.fi}
• 关键词：Formin ; FHOD1 ; Cytoskeleton ; Actin ; Melanoma ; Tumorigenesis ; SRE ; MKL-1 ; MRTF-A ; MAL
• 刊名：Experimental Cell Research
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：350
• 期：1
• 页码：267-278
• 全文大小：1651 K
• 卷排序：350

文摘

The functional properties of actin-regulating formin proteins are diverse and in many cases cell-type specific. FHOD1, a formin expressed predominantly in cells of mesenchymal lineage, bundles actin filaments and participates in maintenance of cell shape, migration and cellular protrusions. FHOD1 participates in cancer-associated epithelial to mesenchymal transition (EMT) in oral squamous cell carcinoma and breast cancer. The role of FHOD1 in melanomas has not been characterized. Here, we show that FHOD1 expression is typically strong in cutaneous melanomas and cultured melanoma cells while the expression is low or absent in benign nevi. By using shRNA to knockdown FHOD1 in melanoma cells, we discovered that FHOD1 depleted cells are larger, rounder and have smaller focal adhesions and inferior migratory capacity as compared to control cells. Importantly, we found FHOD1 depleted cells to have reduced colony-forming capacity and attenuated tumor growth in vivo, a finding best explained by the reduced proliferation rate caused by cell cycle arrest. Unexpectedly, FHOD1 depletion did not prevent invasive growth at the tumor margins. These results suggest that FHOD1 participates in key cellular processes that are dysregulated in malignancy, but may not be essential for melanoma cell invasion.