PMID- 35821094
OWN - NLM
STAT- MEDLINE
DCOM- 20220928
LR  - 20231213
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 102
IP  - 10
DP  - 2022 Oct
TI  - p21-activated kinase 2 binds to transcription factor SOX2 and up-regulates DEK to 
      promote the progression of lung squamous cell carcinoma.
PG  - 1109-1120
LID - S0023-6837(22)00118-0 [pii]
LID - 10.1038/s41374-022-00808-5 [doi]
AB  - Lung squamous cell carcinoma (LSCC) is a prevalent and progressive subtype of 
      lung cancer. This study aimed to substantiate the regulatory effect of the 
      PAK2/SOX2/DEK axis on the LSCC development. LSCC tissues (n = 83) and adjacent 
      normal tissues were collected and SOX2 expression was determined by qRT-PCR and 
      Western blotting. Correlation between SOX2 expression and the prognosis of LSCC 
      patients was then explored utilizing Kaplan-Meier analysis. 
      Co-immunoprecipitation and glutathione-S-transferase pull-down assays were 
      conducted to validate the binding of SOX2 to DEK. Gain- and loss- of function 
      assays were then performed on LSCC cells, with CCK-8 and Transwell assays applied 
      to detect the malignant behaviors of cells. A mouse xenograft model of LSCC was 
      further established for in vivo validation. The expression levels of SOX2, PAK2 
      and DEK were up-regulated in LSCC tissues and cells. SOX2 overexpression was 
      correlated with poor prognosis of LSCC patients. Knockdown of SOX2 weakened the 
      viability and the migratory and invasive potential of LSCC cells. Further, PAK2 
      directly interacted with SOX2. PAK2 overexpression accelerated the malignant 
      phenotypes of LSCC cells through interplay with SOX2. Moreover, SOX2 activated 
      the expression of DEK, and silencing DEK attenuated the malignant behaviors of 
      LSCC cells. In conclusion, PAK2 could bind to the transcription factor SOX2 and 
      thus activate the expression of DEK, thereby driving the malignant phenotypes of 
      LSCC cells both in vivo and in vitro.
CI  - (c) 2022. The Author(s), under exclusive licence to United States and Canadian 
      Academy of Pathology.
FAU - Xie, Shiguang
AU  - Xie S
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanchang University, 330006, Nanchang, P.R. China.
FAU - Wan, Xuan
AU  - Wan X
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanchang University, 330006, Nanchang, P.R. China.
FAU - Chen, Shuyun
AU  - Chen S
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanchang University, 330006, Nanchang, P.R. China.
FAU - Hu, Yan
AU  - Hu Y
AD  - Department of Orthopedics, The First Affiliated Hospital of Nanchang University, 
      330006, Nanchang, P.R. China. ndyfy00494@ncu.edu.cn.
FAU - Liu, Xiaoming
AU  - Liu X
AUID- ORCID: 0000-0002-8643-3477
AD  - Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang 
      University, 330006, Nanchang, P.R. China. ndyfy00620@ncu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220711
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (DEK protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Poly-ADP-Ribose Binding Proteins)
RN  - 0 (SOX2 protein, human)
RN  - 0 (SOXB1 Transcription Factors)
RN  - EC 2.7.11.1 (PAK2 protein, human)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
RN  - GAN16C9B8O (Glutathione)
RN  - M03GIQ7Z6P (Sincalide)
SB  - IM
MH  - Animals
MH  - *Carcinoma, Non-Small-Cell Lung/genetics
MH  - *Carcinoma, Squamous Cell/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Chromosomal Proteins, Non-Histone/genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic
MH  - Glutathione/metabolism
MH  - Humans
MH  - *Laryngeal Neoplasms/genetics/pathology
MH  - Lung/metabolism
MH  - *Lung Neoplasms/genetics/metabolism
MH  - Mice
MH  - *MicroRNAs/genetics
MH  - Oncogene Proteins
MH  - Poly-ADP-Ribose Binding Proteins/genetics/metabolism
MH  - SOXB1 Transcription Factors
MH  - Sincalide/genetics/metabolism
MH  - p21-Activated Kinases/genetics/metabolism
EDAT- 2022/07/13 06:00
MHDA- 2022/09/28 06:00
CRDT- 2022/07/12 23:52
PHST- 2021/01/18 00:00 [received]
PHST- 2022/05/11 00:00 [accepted]
PHST- 2022/04/28 00:00 [revised]
PHST- 2022/07/13 06:00 [pubmed]
PHST- 2022/09/28 06:00 [medline]
PHST- 2022/07/12 23:52 [entrez]
AID - S0023-6837(22)00118-0 [pii]
AID - 10.1038/s41374-022-00808-5 [doi]
PST - ppublish
SO  - Lab Invest. 2022 Oct;102(10):1109-1120. doi: 10.1038/s41374-022-00808-5. Epub 
      2022 Jul 11.