Laminin-111 peptide C16 regulates invadopodia activity of malignant cells through β1 integrin, Src and ERK 1/2.
Laminin-111 peptide C16 regulates invadopodia activity of malignant cells through β1 integrin, Src and ERK 1/2.
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DOI：
10.18632/oncotarget.10062
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发表时间：
2016-07-26
期刊：
影响因子：
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通讯作者：
Jaeger RG
中科院分区：
文献类型：
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作者：
Siqueira AS;Pinto MP;Cruz MC;Smuczek B;Cruz KS;Barbuto JA;Hoshino D;Weaver AM;Freitas VM;Jaeger RG
层粘连蛋白肽影响肿瘤行为。在本研究中，我们探讨了层粘连蛋白肽C16（KAFDITYVRLKF，γ1链）是否会增加鳞状细胞癌（CAL 27）和纤维肉瘤（HT 1080）细胞的侵袭伪足活性。我们发现，C16刺激invadopodia活动随着时间的推移，在两个细胞系。罗丹明结合的C16修饰细胞的边缘，表明可能与膜受体结合。流式细胞术显示，C16增加活化的β1整联蛋白，并且β1整联蛋白miRNA介导的耗竭减少两种细胞系中C16诱导的侵袭伪足活性。C16刺激Src和ERK 1/2磷酸化，并且ERK 1/2抑制降低肽诱导的侵袭伪足活性。C16也增加了两种细胞系中的皮质素磷酸化。基于我们的研究结果，我们认为C16可能通过β1整合素、Src和ERK 1/2信号通路调节鳞状细胞癌和纤维肉瘤细胞侵袭伪足的活性。
Laminin peptides influence tumor behavior. In this study, we addressed whether laminin peptide C16 (KAFDITYVRLKF, γ1 chain) would increase invadopodia activity of cells from squamous cell carcinoma (CAL27) and fibrosarcoma (HT1080). We found that C16 stimulates invadopodia activity over time in both cell lines. Rhodamine-conjugated C16 decorates the edge of cells, suggesting a possible binding to membrane receptors. Flow cytometry showed that C16 increases activated β1 integrin, and β1 integrin miRNA-mediated depletion diminishes C16-induced invadopodia activity in both cell lines. C16 stimulates Src and ERK 1/2 phosphorylation, and ERK 1/2 inhibition decreases peptide-induced invadopodia activity. C16 also increases cortactin phosphorylation in both cells lines. Based on our findings, we propose that C16 regulates invadopodia activity over time of squamous carcinoma and fibrosarcoma cells, probably through β1 integrin, Src and ERK 1/2 signaling pathways.