Evaluation of Hippo Pathway and CD133 in Radiation Resistance in Small-Cell Lung Cancer.

Kui Yang,Ruixiang Tang,Yang Zhao,Yonghao Du

doi:10.1155/2021/8842554

Abstract

Although the Hippo pathway and CD133 have been reported to play pertinent roles in a variety of cancer, knowledge about their contribution to radiation resistance in small-cell lung cancer (SCLC) is limited. In this first-of-a-kind study, we have reported the expression of key Hippo pathway proteins in SCLC patients by immunohistochemical staining. We assessed the involvement of yes-associated protein 1 (YAP1) in radiation resistance by Cell Counting Kit-8 (CCK-8) and flow cytometry. In addition, we analysed the impact of CD133 on radiotherapy for SCLC. The mammalian Ste20-like serine/threonine kinase 2(MST2), pMST2, and pYAP1 in the Hippo pathway were not significantly associated with the disease stage and survival time in patients with SCLC. However, the pYAP1 expression showed some significance in the “YAP/TAZ subgroup” of SCLC patients. The proportion of CD133 in the SCLC cells was controlled by the YAP1 expression. The CD133 and YAP1 levels were significantly correlation with each other in tissues of SCLC patients. We sorted and isolated the CD133+ and CD133−cells in H69 and found that the cell surface glycoprotein may be associated with the radiation resistance of SCLC.In summary, we have firstly reported the expression of key Hippo pathway proteins in SCLC patients. Furthermore, we also identified that CD133 may be controlled by the expression of YAP1 in the Hippo pathway and that CD133 may be associated with the radiation resistance of SCLC.

Highlights

Small-cell lung cancer (SCLC) is an aggressive lung cancer subtype with high recurrence rates and poor outcomes [1]
Our previous study indicated that the phosphorylation of MST2 and yes-associated protein 1 (YAP1) may modulate the multidrug resistance of SCLC [20]
One large-scale screening dataset asserted that a yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) subgroup in the SCLC cell lines may be more susceptible to chemotherapy or targeted therapies [27]

Summary

Introduction

Small-cell lung cancer (SCLC) is an aggressive lung cancer subtype with high recurrence rates and poor outcomes [1]. E Hippo signaling cascade plays various roles in cancer, including the regulation of cell proliferation and apoptosis, progression regulation of stem cell self-renewal, drug resistance, and metastasis [5,6,7]. En, LATS1/2 phosphorylates the core proteins yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) [10]. E YAP/TAZ functionality is controlled via localization within the cells as well as phosphorylation. While the phosphorylated YAP/TAZ are restricted and degraded in the cytosol, their dephosphorylation allows them to enter the nucleus and interact with the key transcription factors, driving tumor proliferation and metastasis [11]. E Hippo pathway is important in various forms of cancers, including in non-SCLC (NSCLC), breast, colon, liver, and stomach cancers [12]. The information about this pathway with regard to SCLC is limited

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