S100A7 promotes lung adenocarcinoma to squamous carcinoma transdifferentiation, and its expression is differentially regulated by the Hippo-YAP pathway in lung cancer cells.
Our previous study revealed that S100A7 was selectively expressed in lung squamous cell carcinoma tissues but not in adenocarcinoma. Thus far, the functions of S100A7 in lung cancer have remained largely unknown. Here, we reveal that S100A7 overexpression facilitates the transdifferentiation from adenocarcinoma (ADC) to squamous carcinoma (SCC) in several lung cancer cells, which is confirmed by an increase in DNp63 expression and a decrease in thyroid transcription factor 1 (TTF1) and aspartic proteinase napsin (napsin A) expression. Further study finds that activation of the Hippo pathway induces S100A7 expression and further confirms that nuclear YAP acts as a repressor of S100A7 in H292 cells. Subsequently, we verify that TEAD1 is required for YAP transcriptional repression of S100A7. More importantly, we determine that S100A7 overexpression partially rescues lung ADC to SCC transdifferentiation inhibited by YAP overexpression in all tested cells, suggesting that S100A7 and YAP have the opposite effects on lung ADC to SCC conversion. Taken together, our study demonstrates for the first time that S100A7 not only functions as a facilitator of adenous-squamous carcinoma phenotypic transition in lung cancer cells but also that its expression is differentially regulated by the Hippo-YAP pathway.
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Rui
R
Wang
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Yunguang
Y
Li
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Enze
E
Hu
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Fei
F
Kong
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Junhao
J
Wang
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Jin
J
Liu
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Qirui
Q
Shao
The Department of Basic Theory, College of Sports, Northwest Normal University, Lanzhou, China.
Ying
Y
Hao
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Dacheng
D
He
Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China.
Xueyuan
X
Xiao
D000072283:A549 Cells; D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D000090683:Hippo Signaling Pathway; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000075023:S100 Calcium Binding Protein A7 / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D000199:Actins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000075023:S100 Calcium Binding Protein A7; C089242:S100A7 protein, human; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D017346:Protein Serine-Threonine Kinases
ADC to SCC transdifferentiation; S100A7; YAP; lung cancer cells; the Hippo pathway