PMID- 33649808
OWN - NLM
STAT- MEDLINE
DCOM- 20210716
LR  - 20240226
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 47
IP  - 5
DP  - 2021 May
TI  - MTSS1 inhibits colorectal cancer metastasis by regulating the CXCR4/CXCL12 
      signaling axis.
LID - 65 [pii]
LID - 10.3892/ijmm.2021.4898 [doi]
AB  - The liver is the most common site of metastasis for colorectal cancer (CRC). 
      Metastasis suppressor 1 (MTSS1), a potential tumor suppressor gene associated 
      with tumor metastasis, has been reported to play an important role in cancer 
      development. The present study aimed to investigate the effects and underlying 
      mechanisms of MTSS1 on the biological behavior of CRC cells both in vitro and 
      in vivo. A CRC mouse model with a high liver metastatic potential was established 
      by injecting mice with SW1116 cells, and the association between MTSS1 expression 
      levels and the metastatic potential of forming liver metastasis lesions was 
      subsequently analyzed. MTSS1 gain‑ and loss‑of‑function experiments were 
      performed by transfecting the CRC cell lines, SW1116 and DLD‑1, with 
      Plvx‑IRES‑ZsGreen1‑MTSS1 plasmid and short hairpin RNA, respectively. Cell 
      proliferation, migration, invasion and cell cycle distribution were analyzed by 
      MTT, Transwell and flow cytometric assays, respectively. To further determine the 
      underlying mechanisms of MTSS1 in CRC, the expression levels of cell surface 
      chemokine C‑X‑C receptor 4 (CXCR4) and its downstream signaling factors, Rac and 
      cell division cycle 42 (CDC42), were analyzed with or without C‑X‑C motif 
      chemokine ligand 12 (CXCL12) stimulation. The results revealed that as the CRC 
      metastatic potential increased, the expression levels of MTSS1 decreased. The 
      overexpression of MTSS1 exerted an inhibitory effect on cell proliferation, 
      migration and invasion, while the knockdown of MTSS1 exerted the opposite effects 
      in vitro. Flow cytometric analysis and western blot analysis demonstrated that 
      MTSS1 negatively regulated the expression levels of cell surface CXCR4 and its 
      downstream signaling pathway activation. On the whole, the results of the present 
      study indicate that MTSS1 may play an important negative role in CRC metastasis 
      and the underlying mechanisms may involve the downregulation of the CXCR4/CXCL12 
      signaling axis.
FAU - Chen, Lei
AU  - Chen L
AD  - Department of Oncology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu 215004, P.R. China.
FAU - Chen, Qiang
AU  - Chen Q
AD  - Department of General Surgery, The Second Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215004, P.R. China.
FAU - Wu, Yongyou
AU  - Wu Y
AD  - Department of General Surgery, The Second Affiliated Hospital of Soochow 
      University, Suzhou, Jiangsu 215004, P.R. China.
FAU - Zhu, Minggao
AU  - Zhu M
AD  - Department of Oncology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu 215004, P.R. China.
FAU - Hu, Jia
AU  - Hu J
AD  - Department of Genetics and Bioinformatics, College of Basic Medicine and 
      Biological Sciences of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
FAU - Zhuang, Zhixiang
AU  - Zhuang Z
AD  - Department of Oncology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu 215004, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Retracted Publication
DEP - 20210302
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (MTSS1 protein, human)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, CXCR4)
RN  - 50SG953SK6 (Mitomycin)
RN  - Q20Q21Q62J (Cisplatin)
RN  - UM20QQM95Y (Ifosfamide)
RN  - MIP protocol
SB  - IM
RIN - Int J Mol Med. 2023 Feb;51(2):. PMID: 36601756
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Chemokine CXCL12/genetics/*metabolism
MH  - Cisplatin
MH  - Colorectal Neoplasms/genetics/*metabolism/pathology
MH  - HT29 Cells
MH  - Humans
MH  - Ifosfamide
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Microfilament Proteins/genetics/*metabolism
MH  - Mitomycin
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Receptors, CXCR4/genetics/*metabolism
MH  - *Signal Transduction
MH  - Mice
PMC - PMC7952249
OTO - NOTNLM
OT  - colorectal cancer
OT  - metastasis
OT  - MTSS1
OT  - CXCR4/CXCL12 axis
COIS- The authors declare that they have no competing interests.
EDAT- 2021/03/03 06:00
MHDA- 2021/07/17 06:00
PMCR- 2021/02/26
CRDT- 2021/03/02 06:20
PHST- 2020/10/09 00:00 [received]
PHST- 2021/02/04 00:00 [accepted]
PHST- 2021/03/02 06:20 [entrez]
PHST- 2021/03/03 06:00 [pubmed]
PHST- 2021/07/17 06:00 [medline]
PHST- 2021/02/26 00:00 [pmc-release]
AID - 65 [pii]
AID - ijmm-47-05-04898 [pii]
AID - 10.3892/ijmm.2021.4898 [doi]
PST - ppublish
SO  - Int J Mol Med. 2021 May;47(5):65. doi: 10.3892/ijmm.2021.4898. Epub 2021 Mar 2.