YAP1 promotes multidrug resistance of small cell lung cancer by CD74-related signaling pathways
Yongchun Song1, Yanqin Sun2, Yingying Lei3
1Department of Oncology Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Background:
Our previous research found that YAP1 may have a role in multidrug resistance (MDR) in small cell lung cancer (SCLC). However, its underlying mechanism is unknown.
Methods:
In this study, we investigated the expression of YAP1 using immunohistochemical staining and assessed the relationship between the expression of YAP1 and overall survival in patients with SCLC. We established H69 stable cell lines that overexpressed constitutively active YAP1 and H446 stable cell lines that dominate negative YAP1. We conducted CCK-8, flow cytometric analysis, and in vivo chemosensitivity experiments to evaluate the function of YAP1 in drug sensitivity apoptosis in vitro and in vivo.
Results:
The results indicated that patients with high YAP1 expression have shorter survival rates and more advanced disease stage than those with low YAP1 expression. YAP1 may induce MDR by inhibiting the apoptosis of SCLC. YAP1 induced MDR when YAP1 was hyperactivated, and drug sensitivity increased when YAP1 was inhibited in vitro and in vivo. CD74 was significantly correlated with YAP1 in SCLC samples. Inhibition of CD74 using ISO-1 increased drug sensitivity significantly.
Conclusions:
The expression of YAP1 is significantly correlated with overall survival and disease stage in patients with SCLC. YAP1 may play an important role in these patients. We were the first to report that YAP1 can induce MDR in SCLC in vitro and in vivo. CD74 may be involved in YAP1-induced MDR.
More Related Videos
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
09:55All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The Intrinsic Apoptotic Pathway
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Treatment Resistant Cancers
