PMID- 33710818
OWN - NLM
STAT- Publisher
LR  - 20240222
IS  - 2095-3941 (Print)
IS  - 2095-3941 (Linking)
VI  - 18
IP  - 3
DP  - 2021 Mar 12
TI  - FGFR/RACK1 interacts with MDM2, promotes P53 degradation, and inhibits cell 
      senescence in lung squamous cell carcinoma.
PG  - 665-74
LID - j.issn.2095-3941.2020.0389 [pii]
LID - 10.20892/j.issn.2095-3941.2020.0389 [doi]
AB  - OBJECTIVE: FGFR is considered an important driver gene of lung squamous cell 
      carcinoma (LSCC). Thus, identification of the biological events downstream of 
      FGFR is important for the treatment of this malignancy. Our previous study has 
      shown that the FGFR/RACK1 complex interacts with PKM2 and consequently promotes 
      glycolysis in LSCC cells. However, the biological functions of the FGFR/RACK1 
      complex remain poorly understood. METHODS: Anchorage-independent assays and in 
      vivo tumorigenesis assays were performed to evaluate cancer cell malignancy. 
      Distant seeding assays were performed to evaluate cancer cell metastasis. beta-gal 
      staining was used to examine cell senescence, and immunoprecipitation assays were 
      performed to examine the interactions among FGFR, RACK1, and MDM2. RESULTS: 
      FGFR/RACK1 was found to regulate the senescence of LSCC cells. Treatment with 
      PD166866, an inhibitor of FGFR, or knockdown of RACK1 induced senescence in LSCC 
      cells (P < 0.01). A molecular mechanistic study showed that FGFR/RACK1/MDM2 form 
      a complex that promotes the degradation of p53 and thus inhibits cell senescence. 
      PD166866 and RG7112, an MDM2/p53 inhibitor, cooperatively inhibited the colony 
      formation and distal seeding of LSCC cells (P < 0.01), and upregulated the 
      expression of p53 and p21. CONCLUSIONS: Together, our findings revealed the 
      regulatory roles and mechanisms of FGFR/RACK1 in cell senescence. This 
      understanding should be important in the treatment of LSCC.
CI  - Copyright (c) 2021 Cancer Biology & Medicine.
FAU - Chen, Tao
AU  - Chen T
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
FAU - Wang, Fei
AU  - Wang F
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
FAU - Wei, Shupei
AU  - Wei S
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
FAU - Nie, Yingjie
AU  - Nie Y
AD  - NHC Key Laboratory of Pulmonary Immunological Diseases, Clinical Research Lab 
      Center, Guizhou Provincial People's Hospital, Guiyang OK 550002, China.
FAU - Zheng, Xiaotao
AU  - Zheng X
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
FAU - Deng, Yu
AU  - Deng Y
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
FAU - Zhu, Xubin
AU  - Zhu X
AD  - Longgang Central Hospital of Shenzhen, Affiliated Shenzhen Longgang Central 
      Hospital of Zunyi Medical College, Shenzhen 518116, China.
FAU - Deng, Yuezhen
AU  - Deng Y
AD  - Center for Molecular Medicine, Xiangya Hospital, Central South University, 
      Changsha 410078, China.
FAU - Zhong, Nanshan
AU  - Zhong N
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
FAU - Zhou, Chengzhi
AU  - Zhou C
AUID- ORCID: 0000-0003-0029-6879
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
LA  - eng
GR  - 81972163/National Natural Science Foundation of China/
GR  - 2019A1515010947/Guangdong Provincial Department of Science and Technology/
GR  - SKLRDQN201702/State Key Lab of Respiratory Disease/
GR  - SKLRD-OP-202003/State Key Lab of Respiratory Disease/
GR  - 2017-21020/Guangdong High Level University Clinical Cultivation Project/
GR  - 320.6750.18125/Wu Jieping Medical Foundation/
GR  - 320.6750.19088-8/Wu Jieping Medical Foundation/
GR  - 2019PT320003/Nonprofit Central Research Institute Fund of the Chinese Academy of 
      Medical Sciences/
PT  - Journal Article
DEP - 20210312
PL  - China
TA  - Cancer Biol Med
JT  - Cancer biology & medicine
JID - 101588850
SB  - IM
PMC - PMC8330524
OTO - NOTNLM
OT  - FGFR
OT  - MDM2
OT  - P53
OT  - RACK1
OT  - senescence
COIS- No potential conflicts of interest are disclosed.
EDAT- 2021/03/13 06:00
MHDA- 2021/03/13 06:00
PMCR- 2021/08/15
CRDT- 2021/03/12 13:05
PHST- 2021/03/12 13:05 [entrez]
PHST- 2021/03/13 06:00 [pubmed]
PHST- 2021/03/13 06:00 [medline]
PHST- 2021/08/15 00:00 [pmc-release]
AID - j.issn.2095-3941.2020.0389 [pii]
AID - 10.20892/j.issn.2095-3941.2020.0389 [doi]
PST - aheadofprint
SO  - Cancer Biol Med. 2021 Mar 12;18(3):665-74. doi: 
      10.20892/j.issn.2095-3941.2020.0389.