Abstract

Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, and the identification of the apoptotic process of NSCLC is vital for its treatment. Usually, both the expression level and the cell surface level of TNFRSF10B (TNF Receptor superfamily member 10B) will increase after treatment with some chemotherapeutic agents, which plays a critical role in the apoptosis induction. However, the exact molecular mechanism underlying TNFRSF10B regulation remains largely elusive. Here, we found that TNFRSF10B, along with a vesicular trafficking regulator protein, YIPF2, were upregulated after treatment with pemetrexed (PEM) in NSCLC cells. Besides, YIPF2 increased the surface level of TNFRF10B, while YIPF2 knockdown inhibited the upregulation of TNFRSF10B and its recycling to plasma membrane. In addition, RAB8 decreased the cell surface TNFRSF10B by promoting its removing from plasma membrane to cytoplasm. Furthermore, we found that YIPF2, RAB8 and TNFRSF10B proteins interacted physically with each other. YIPF2 could further inhibit the physical interaction between TNFRSF10B and RAB8, thereby suppressing the removing of TNFRSF10B from plasma membrane to cytoplasm mediated by RAB8 and maintaining its high level on cell surface. Finally, using bioinformatics database, the YIPF2-TNFRSF10B axis was confirmed to be associated with the malignant progression of lung cancer. Taken together, we show that YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in NSCLC cells. These findings may be beneficial for the development of potential prognostic markers of NSCLC and may provide effective treatment strategy.

Details

Title
YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in non-small cell lung cancer cells
Author
Wang, Yingying 1   VIAFID ORCID Logo  ; Sen, Guo 1   VIAFID ORCID Logo  ; Li, Dongmei 1 ; Tang Yongkang 1 ; Li, Lei 1 ; Su, Ling 1 ; Liu Xiangguo 1   VIAFID ORCID Logo 

 Shandong University, Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Qingdao, China (GRID:grid.27255.37) (ISNI:0000 0004 1761 1174) 
Publication year
2020
Publication date
Apr 2020
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2391205414
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.