S100A7 promotes lung adenocarcinoma to squamous carcinoma transdifferentiation, and its expression is differentially regulated by the Hippo-YAP pathway in lung cancer cells

Wang, Rui; Li, Yunguang; Hu, Enze; Kong, Fei; Wang, Junhao; Liu, Jin; Shao, Qirui; Hao, Ying; He, Dacheng; Xiao, Xueyuan

doi:10.18632/oncotarget.15063

Cited by 13 publications

(8 citation statements)

References 42 publications

(69 reference statements)

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“…A panel of lung adenocarcinoma cell lines without targetable genetic alterations, including a KRAS wild‐type (H322), three KRAS mutant (A549, H358 and H460) and a KRAS wild‐type adenocarcinoma‐like mucoepidermoid carcinoma cell line (H292) , was selected to further investigate the relationship between EGFR and IFNγ pathway activation with PD‐L1 expression. Membrane PD‐L1 was observed in all cell lines, irrespective of KRAS mutation status (see supplementary material, Figure S2A).…”

Section: Resultsmentioning

confidence: 99%

MAPK pathway activity plays a key role in PD‐L1 expression of lung adenocarcinoma cells

Stutvoet

Kol

Vries

et al. 2019

The Journal of Pathology

131

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Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) have improved the survival of patients with non‐small cell lung cancer (NSCLC). Still, many patients do not respond to these inhibitors. PD‐L1 (CD274) expression, one of the factors that influences the efficacy of immune checkpoint inhibitors, is dynamic. Here, we studied the regulation of PD‐L1 expression in NSCLC without targetable genetic alterations in EGFR, ALK, BRAF, ROS1, MET, ERBB2 and RET. Analysis of RNA sequencing data from these NSCLCs revealed that inferred IFNγ, EGFR and MAPK signaling correlated with CD274 gene expression in lung adenocarcinoma. In a representative lung adenocarcinoma cell line panel, stimulation with EGF or IFNγ increased CD274 mRNA and PD‐L1 protein and membrane levels, which were further enhanced by combining EGF and IFNγ. Similarly, tumor cell PD‐L1 membrane levels increased after coculture with activated peripheral blood mononuclear cells. Inhibition of the MAPK pathway, using EGFR inhibitors cetuximab and erlotinib or the MEK 1 and 2 inhibitor selumetinib, prevented EGF‐ and IFNγ‐induced CD274 mRNA and PD‐L1 protein and membrane upregulation, but had no effect on IFNγ‐induced MHC‐I upregulation. Interestingly, although IFNγ increases transcriptional activity of CD274, MAPK signaling also increased stabilization of CD274 mRNA. In conclusion, MAPK pathway activity plays a key role in EGF‐ and IFNγ‐induced PD‐L1 expression in lung adenocarcinoma without targetable genetic alterations and may present a target to improve the efficacy of immunotherapy. © 2019 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Section: Resultsmentioning

confidence: 99%

MAPK pathway activity plays a key role in PD‐L1 expression of lung adenocarcinoma cells

Stutvoet

Kol

Vries

et al. 2019

The Journal of Pathology

131

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“…In vitro, Wang et al demonstrated that S100A7 expression was induced by the Hippo pathway and depletion of S100A7 lead to suppression of DNp63, a marker for SSC, while the ADC markers TFF1 and napsin A were upregulated, and an inverse correlation of S100A7 and yes-associated protein (YAP) was observed. In summary, these data implicate that S100A7 is an essential player in cellular plasticity and ADC to SSC transdifferentiation [ 120 ].…”

Section: S100 Proteins In Cancermentioning

confidence: 99%

Friend or Foe: S100 Proteins in Cancer

Allgöwer

Kretz

Karstedt

et al. 2020

Cancers

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S100 proteins are widely expressed small molecular EF-hand calcium-binding proteins of vertebrates, which are involved in numerous cellular processes, such as Ca2+ homeostasis, proliferation, apoptosis, differentiation, and inflammation. Although the complex network of S100 signalling is by far not fully deciphered, several S100 family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer. The research of the past decades revealed that S100 proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma. Hence, S100 family members have also been shown to be promising diagnostic markers and possible novel targets for therapy. However, the current knowledge of S100 proteins is limited and more attention to this unique group of proteins is needed. Therefore, this review article summarises S100 proteins and their relation in different cancer types, while also providing an overview of novel therapeutic strategies for targeting S100 proteins for cancer treatment.

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“…Through interactions with ΔNp63, YAP can act as an important barrier for phenotypic plasticity in lung cancer. YAP-ΔNp63 interaction can block YAP-TEAD mediated transcriptional repression of S100A7, a factor that is important for the transition process of lung adenocarcinoma to squamous carcinoma trans-differentiation in lung cancer cells (Li et al, 2017; Wang et al, 2017). Conversely, YAP represses ΔNp63 via transcriptional regulation of ZEB2 expression, to inhibit squamous cell trans-differentiation in Lkb1-deficient lung cancer cells (Gao et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Reciprocal Crosstalk Between YAP1/Hippo Pathway and the p53 Family Proteins: Mechanisms and Outcomes in Cancer

Raj

Bam

2019

Front. Cell Dev. Biol.

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The YAP1/Hippo and p53 pathways are critical protectors of genome integrity in response to DNA damage. Together, these pathways secure cellular adaptation and maintain overall tissue integrity through transcriptional re-programing downstream of various environmental and biological cues generated during normal tissue growth, cell proliferation, and apoptosis. Genetic perturbations in YAP1/Hippo and p53 pathways are known to contribute to the cells’ ability to turn rogue and initiate tumorigenesis. The Hippo and p53 pathways cooperate on many levels and are closely coordinated through multiple molecular components of their signaling pathways. Several functional and physical interactions have been reported to occur between YAP1/Hippo pathway components and the three p53 family members, p53, p63, and p73. Primarily, functional status of p53 family proteins dictates the subcellular localization, protein stability and transcriptional activity of the core component of the Hippo pathway, Yes-associated protein 1 (YAP1). In this review, we dissect the critical points of crosstalk between the YAP1/Hippo pathway components, with a focus on YAP1, and the p53 tumor suppressor protein family. For each p53 family member, we discuss the biological implications of their interaction with Hippo pathway components in determining cell fate under the conditions of tissue homeostasis and cancer pathogenesis.

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S100A7 promotes lung adenocarcinoma to squamous carcinoma transdifferentiation, and its expression is differentially regulated by the Hippo-YAP pathway in lung cancer cells

Cited by 13 publications

References 42 publications

MAPK pathway activity plays a key role in PD‐L1 expression of lung adenocarcinoma cells

MAPK pathway activity plays a key role in PD‐L1 expression of lung adenocarcinoma cells

Friend or Foe: S100 Proteins in Cancer

Reciprocal Crosstalk Between YAP1/Hippo Pathway and the p53 Family Proteins: Mechanisms and Outcomes in Cancer

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