ERK phosphorylation is dependent on cell adhesion in a subset of pediatric sarcoma cell lines.
ERK phosphorylation is dependent on cell adhesion in a subset of pediatric sarcoma cell lines.
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DOI：
10.1016/j.bbamcr.2022.119264
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发表时间：
2022-04
期刊：
影响因子：
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通讯作者：
H. Yoon;Ben Y. Maron;Sofia Girald-Berlingeri;A. Gasilina;Josephine Gollin;X. Jian;Itoro Akpan;M. Yohe;P. Randazzo;Pei-Wen Chen
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作者：
H. Yoon;Ben Y. Maron;Sofia Girald-Berlingeri;A. Gasilina;Josephine Gollin;X. Jian;Itoro Akpan;M. Yohe;P. Randazzo;Pei-Wen Chen
骨肉瘤（OS）和Pax-Foxo 1融合阴性横纹肌肉瘤（FN-RMS）是儿童肉瘤，在晚期疾病患者中表现较差。在这两种恶性肿瘤中，肌动蛋白结合蛋白与预后不良有关。整合素粘附复合物（IACs）与肌动蛋白网络紧密偶联，并且IACs介导的信号传导与癌症的进展有关。然而，IAC和肌动蛋白细胞骨架重塑与细胞信号传导的关系在儿科肉瘤中研究不足。在这里，我们测试的假设，IAC动态影响ERK激活OS和FN-RMS细胞系。ERK激活的粘附依赖性在OS和FN-RMS细胞中不同。在OS细胞系中，粘附对磷酸化ERK（pERK）没有一致的影响。响应于胎牛血清或1 ng/ml EGF的ERK磷酸化在OS细胞系和一种悬浮的FN-RMS细胞系中几乎与粘附于聚-L-赖氨酸（PL）或纤连蛋白（FN）的细胞一样有效。相比之下，塑料，PL或FN的粘附增加ERK磷酸化，并大于添加剂与1 ng/ml的EGF在三个FN-RMS细胞系中暴露15分钟。pERK的增加部分依赖于FAK和PAK 1/2，但独立于IAC成熟。据我们所知，这种粘附依赖性信号的检查是第一次在儿科肉瘤，并导致发现的差异，从流行的范例和细胞系之间的信号通路中的组件之间的耦合程度的差异。
Osteosarcoma (OS) and Pax-Foxo1 fusion negative rhabdomyosarcoma (FN-RMS) are pediatric sarcomas with poor prognoses in patients with advanced disease. In both malignancies, an actin binding protein has been linked to poor prognosis. Integrin adhesion complexes (IACs) are closely coupled to actin networks and IAC-mediated signaling has been implicated in the progression of carcinomas. However, the relationship of IACs and actin cytoskeleton remodeling with cell signaling is understudied in pediatric sarcomas. Here, we tested the hypothesis that IAC dynamics affect ERK activation in OS and FN-RMS cell lines. Adhesion dependence of ERK activation differed among the OS and FN-RMS cells examined. In the OS cell lines, adhesion did not have a consistent effect on phospho-ERK (pERK). ERK phosphorylation in response to fetal calf serum or 1 ng/ml EGF was nearly as efficient in OS cell lines and one FN-RMS cell line in suspension as cells adherent to poly-l-lysine (PL) or fibronectin (FN). By contrast, adhesion to plastic, PL or FN increased ERK phosphorylation and was greater than additive with a 15 min exposure to 1 ng/ml EGF in three FN-RMS cell lines. Increases in pERK were partly dependent on FAK and PAK1/2 but independent of IAC maturation. As far as we are aware, this examination of adhesion-dependent signaling is the first in pediatric sarcomas and has led to the discovery of differences from the prevailing paradigms and differences in the degree of coupling between components in the signaling pathways among the cell lines.