期刊
CANCER LETTERS
卷 523, 期 -, 页码 182-194出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.10.008
关键词
Rab1A; Metastasis; Lung cancer; Interleukin receptor 4; JAK1 inhibitor
类别
资金
- National Natural Science Foundation of China [81871862, 82072638]
- Shanghai International Cooperation Foundation [18410720200]
This study found that Rab1A overexpression in non-small cell lung cancer is significantly correlated with aggressive tumor growth and metastasis by activating the JAK1/STAT6 signaling pathway. Additionally, Rab1A levels also impact sensitivity to JAK1 inhibitors, potentially enhancing the efficacy of JAK1-targeted cancer therapy.
Rab1A overexpression has been observed in several cancer types, however, its significance and the underlying mechanisms in non-small cell lung cancer (NSCLC) remain largely unexplored. This study demonstrated that Rab1A overexpression in NSCLC was significantly correlated to short survival and metastasis. Rab1A overexpression promoted cancer cell migration, invasion, and metastasis both in vitro and in vivo, by activating JAK1/STAT6 signaling through stabilizing IL-4R alpha protein. Strikingly, high Rab1A level was associated with sensitivity to JAK1 inhibitor, and Rab1A overexpression rendered cancer cells vulnerable to JAK1-targeted agents. JAK1 inhibitor, Itacitinib adipate, dramatically inhibited high Rab1A NSCLC metastasis, in both cell line and patient derived xenograft models. Collectively, these findings demonstrated that Rab1A plays a critical role in the aggressive properties of NSCLC, revealing a unique mechanism by which it promotes metastasis. In addition, we found that Rab1A is a determinant of JAK1 inhibitor sensitivity, which could be explored for improving JAK1-targeted cancer therapy.
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