YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in non-small cell lung cancer cells

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 agentmediated 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.

Development and Validation of a TNF Family-Based Signature for Predicting Prognosis, Tumor Immune Characteristics, and Immunotherapy Response in Colorectal Cancer Patients

“…As a result, eight genes (TNFRSF10B, LTBR, TNFRSF10C, TNFSF11, TNFRSF19, NGFR, TNFRSF11A, and TNFRSF25) were used to establish the TFS. TNFRSF10B (also known as DR5 or TRAILR2) is a protein that belongs to the TNFRSF family and mediates the extrinsic apoptotic pathway in various cancer cells [27]. Recent studies revealed that upregulation of this protein in human CRC cells enhanced the efficiency of cancer therapy [28][29][30].…”

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

“…YIPF2 facilitated chemotherapeutic drug-mediated apoptosis by promoting TNFRSF10B cell membrane circulation in NSCLC. 66 ASTX660 as a cIAP1/2 and X-linked inhibitor of apoptosis protein (XIAP) antagonist could sensitize murine oral cancer (MOC1) cells to TNF-α and induce apoptosis of TNFR superfamily downstream cells. Besides, ASTX660 combined with cisplatin and PD-1 blockade could delay tumor growth.…”

The Effect of Necroptosis-related Gene Signature on the Progression, Prognosis, and Immune Microenvironment of Low-grade Glioma

“…In NSCLC tissues, CircRNF20 aggravates the progression of non-small cell lung cancer by activating MAPK9 [37]. YIPF2 can enhance the recirculation of TNFRSF10B to the plasma membrane in non-small cell lung cancer cells, thus promote chemotherapeutic-mediated apoptosis [38]. The reports of these genes in LGG are not complete, and further analysis is needed to explore their effects.…”