PMID- 34258151
OWN - NLM
STAT- MEDLINE
DCOM- 20220105
LR  - 20231107
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 8
IP  - 13
DP  - 2021 Jul
TI  - circFAT1 Promotes Cancer Stemness and Immune Evasion by Promoting STAT3 
      Activation.
PG  - 2003376
LID - 10.1002/advs.202003376 [doi]
LID - 2003376
AB  - Cancer stemness and immune evasion are closely associated, and play critical 
      roles in tumor development and resistance to immunotherapy. However, little is 
      known about the underlying molecular mechanisms that coordinate this association. 
      Here, it is reported that elevated circular RNA FAT1 (circFAT1) in squamous cell 
      carcinoma (SCC) unifies and regulates the positive association between cancer 
      stemness and immune evasion by promoting STAT3 activation. circFAT1 knockdown 
      (KD) reduces tumorsphere formation of SCC cells in vitro and tumor growth in 
      vivo. Bioinformatic analysis reveals that circFAT1 KD impairs the cancer stemness 
      signature and activates tumor cell-intrinsic immunity. Mechanistically, circFAT1 
      binding to STAT3 in the cytoplasm prevents STAT3 dephosphorylation by SHP1 and 
      promotes STAT3 activation, resulting in inhibition of STAT1-mediated 
      transcription. Moreover, circFAT1 KD significantly enhances PD1 blockade 
      immunotherapy by promoting CD8(+) cell infiltration into tumor microenvironment. 
      Taken together, the results demonstrate that circFAT1 is an important regulator 
      of cancer stemness and antitumor immunity.
CI  - (c) 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Jia, Lingfei
AU  - Jia L
AD  - Jonsson Comprehensive Cancer Center UCLA Los Angeles CA 90095 USA.
AD  - Laboratory of Molecular Signaling Division of Oral Biology and Medicine School of 
      Dentistry UCLA Los Angeles CA 90095 USA.
FAU - Wang, Yilun
AU  - Wang Y
AD  - Jonsson Comprehensive Cancer Center UCLA Los Angeles CA 90095 USA.
AD  - Laboratory of Molecular Signaling Division of Oral Biology and Medicine School of 
      Dentistry UCLA Los Angeles CA 90095 USA.
FAU - Wang, Cun-Yu
AU  - Wang CY
AUID- ORCID: 0000-0002-3885-5149
AD  - Jonsson Comprehensive Cancer Center UCLA Los Angeles CA 90095 USA.
AD  - Laboratory of Molecular Signaling Division of Oral Biology and Medicine School of 
      Dentistry UCLA Los Angeles CA 90095 USA.
AD  - Department of Bioengineering Henry Samueli School of Engineering and Applied 
      Science UCLA Los Angeles CA 90095 USA.
LA  - eng
GR  - R01 CA236878/CA/NCI NIH HHS/United States
GR  - R01 DE015964/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210502
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
RN  - 0 (Cadherins)
RN  - 0 (FAT1 protein, human)
RN  - 0 (RNA, Circular)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
SB  - IM
MH  - Animals
MH  - Cadherins/*genetics/immunology/metabolism
MH  - Cell Line, Tumor
MH  - Disease Models, Animal
MH  - Female
MH  - Head and Neck Neoplasms/*genetics/*immunology/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Neoplastic Stem Cells/immunology/metabolism
MH  - RNA, Circular/genetics/immunology/metabolism
MH  - STAT3 Transcription Factor/*genetics/immunology/metabolism
MH  - Signal Transduction/genetics/immunology
MH  - Squamous Cell Carcinoma of Head and Neck/*genetics/*immunology/metabolism
MH  - Tumor Microenvironment/genetics/immunology
PMC - PMC8261519
OTO - NOTNLM
OT  - PD1 blockade
OT  - STAT3
OT  - cancer stem cells
OT  - circFAT1
OT  - circRNA
OT  - head and neck squamous cell carcinoma
OT  - immune evasion
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/15 06:00
MHDA- 2022/01/06 06:00
PMCR- 2021/05/02
CRDT- 2021/07/14 07:07
PHST- 2020/09/03 00:00 [received]
PHST- 2020/11/27 00:00 [revised]
PHST- 2021/07/14 07:07 [entrez]
PHST- 2021/07/15 06:00 [pubmed]
PHST- 2022/01/06 06:00 [medline]
PHST- 2021/05/02 00:00 [pmc-release]
AID - ADVS2378 [pii]
AID - 10.1002/advs.202003376 [doi]
PST - epublish
SO  - Adv Sci (Weinh). 2021 May 2;8(13):2003376. doi: 10.1002/advs.202003376. 
      eCollection 2021 Jul.