Ubiquilin (UBQLN) proteins are involved in diverse cellular processes like endoplasmic reticulum‐associated degradation, autophagy, apoptosis, and epithelial‐to‐mesenchymal transition. UBQLNs interact with a variety of substrates, including cell surface receptors, transcription factor regulators, proteasomal machinery proteins, and transmembrane proteins. In addition, previous work from our lab shows that UBQLN1 interacts with insulin‐like growth factor receptor family members (IGF1R, IGF2R, and INSR) and this interaction regulates the activity and proteostasis of IGFR family members. We wondered whether UBQLN proteins could also bind and regulate additional receptor tyrosine kinases. Thus, we investigated a link between UBQLN and the oncogene epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells. Loss of UBQLN1 occurs at high frequency in human lung cancer patient samples and we have shown that the loss of UBQLN1 is capable of altering processes involved in cell proliferation, migration, invasion, and epithelial‐to‐mesenchymal transition in lung adenocarcinoma cell lines. Here, we present data that loss of UBQLN1 resulted in increased turnover of total EGFR while increasing the relative amount of phosphorylated EGFR in lung adenocarcinoma cells, especially in the presence of its ligand EGF. Furthermore, the loss of UBQLN1 led to a more invasive cell phenotype as manifested by increased proliferation, migration, and speed of movement of these lung adenocarcinoma cells. Taken together, UBQLN1 regulates the expression and stability of EGFR in lung cancer cells.

中文翻译：

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泛素蛋白调节肺腺癌细胞中的 EGFR 水平和活性。

泛素 (UBQLN) 蛋白参与多种细胞过程，如内质网相关降解、自噬、细胞凋亡和上皮间质转化。UBQLN 与多种底物相互作用，包括细胞表面受体、转录因子调节剂、蛋白酶体机制蛋白和跨膜蛋白。此外，我们实验室之前的工作表明，UBQLN1 与胰岛素样生长因子受体家族成员（IGF1R、IGF2R 和 INSR）相互作用，这种相互作用调节 IGFR 家族成员的活性和蛋白质稳态。我们想知道 UBQLN 蛋白是否也可以结合和调节其他受体酪氨酸激酶。因此，我们研究了肺腺癌细胞中 UBQLN 与癌基因表皮生长因子受体 (EGFR) 之间的联系。在人类肺癌患者样本中，UBQLN1 的缺失发生频率很高，我们已经表明，UBQLN1 的缺失能够改变肺腺癌细胞系中涉及细胞增殖、迁移、侵袭和上皮间质转化的过程。在这里，我们提供的数据表明，UBQLN1 的缺失导致总 EGFR 的周转增加，同时增加了肺腺癌细胞中磷酸化 EGFR 的相对量，特别是在其配体 EGF 存在的情况下。此外，UBQLN1 的缺失导致更具侵袭性的细胞表型，表现为这些肺腺癌细胞的增殖、迁移和运动速度增加。总之，UBQLN1 调节肺癌细胞中 EGFR 的表达和稳定性。