PMID- 34975297
OWN - NLM
STAT- MEDLINE
DCOM- 20220323
LR  - 20220323
IS  - 1449-1907 (Electronic)
IS  - 1449-1907 (Linking)
VI  - 19
IP  - 1
DP  - 2022
TI  - Human alpha-defensin 6 (HD6) suppresses CRC proliferation and metastasis through 
      abolished EGF/EGFR signaling pathway.
PG  - 34-46
LID - 10.7150/ijms.64850 [doi]
AB  - The incidence of colorectal cancer (CRC) has increased significantly in the past 
      decade. Early diagnosis and new therapeutics are still urgently needed for CRC in 
      clinical practice. Human alpha-defensin 6 (HD6) plays a defense role against microbes 
      in the gastrointestinal tract. However, the role and mechanism of HD6 in CRC is 
      still unresolved. Specimens from CRC patients with higher HD6 showed better 
      outcomes. Overexpressed HD6 in CRC cells caused a reduction of cell 
      proliferative, migratory, and invasive ability in vitro and in vivo. 
      HD6-overexpressed caused S phase arrest through changes in cyclin-A and B and 
      CDK2 levels. In addition, serpine-1 may be negatively regulated by HD6 altering 
      the translocation of c-Jun N-terminal kinases (JNK), extracellular regulated 
      protein kinases (ERK), and p38. Higher HD6 and lower serpine-1 levels in CRC 
      patients reflected better outcomes. Finally, we found that HD6 interacts directly 
      with epidermal growth factor receptor (EGFR) by co-immunoprecipitated assay. EGF 
      treatment caused an increase of the level of serpine-1 and pEGFR levels and then 
      increased growth activity in HD6 overexpressing cells. Together, our study shows 
      that HD6 may compete with EGF to bind to EGFR and interrupt cancer progression in 
      CRC. We believe these findings may give new insights for HD6 in CRC therapy.
CI  - (c) The author(s).
FAU - Wei, Po-Li
AU  - Wei PL
AD  - Division of Colorectal Surgery, Department of Surgery, Taipei Medical University 
      Hospital, Taipei Medical University, Taipei, Taiwan.
AD  - Department of Surgery, College of Medicine, School of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
AD  - Cancer Research Center and Translational Laboratory, Department of Medical 
      Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, 
      Taiwan.
AD  - Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical 
      University, Taipei, Taiwan.
FAU - Lin, Jang-Chun
AU  - Lin JC
AD  - Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, 
      Taipei, Taiwan.
AD  - Department of Radiology, School of Medicine, College of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
FAU - Hung, Chin-Sheng
AU  - Hung CS
AD  - Department of Surgery, College of Medicine, School of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
FAU - Makondi, Precious Takondwa
AU  - Makondi PT
AD  - Kamuzu Central Hospital - National Cancer Center, Lilongwe, Malawi.
FAU - Batzorig, Uyanga
AU  - Batzorig U
AD  - Department of Surgery, College of Medicine, School of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
FAU - Chang, Tung-Cheng
AU  - Chang TC
AD  - Department of Surgery, College of Medicine, School of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
AD  - Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei 
      Medical University, Taipei, Taiwan.
AD  - Division of Colon and Rectal, Department of Surgery, Shuang Ho Hospital, Taipei 
      Medical University, Taipei, Taiwan.
FAU - Huang, Chien-Yu
AU  - Huang CY
AD  - Department of Surgery, College of Medicine, School of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
AD  - Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei 
      Medical University, Taipei, Taiwan.
AD  - Division of Colon and Rectal, Department of Surgery, Shuang Ho Hospital, Taipei 
      Medical University, Taipei, Taiwan.
FAU - Chang, Yu-Jia
AU  - Chang YJ
AD  - Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, 
      Taipei Medical University, Taipei, Taiwan.
AD  - Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei 
      Medical University, Taipei, Taiwan.
AD  - Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, 
      Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20220101
PL  - Australia
TA  - Int J Med Sci
JT  - International journal of medical sciences
JID - 101213954
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DEFA6 protein, human)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (SERPINE1 protein, human)
RN  - 0 (alpha-Defensins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor
MH  - Cell Cycle Checkpoints
MH  - Cell Proliferation
MH  - Colorectal Neoplasms/*metabolism/*pathology
MH  - Disease Models, Animal
MH  - Epidermal Growth Factor/genetics/*metabolism
MH  - Epithelial-Mesenchymal Transition/physiology
MH  - ErbB Receptors/genetics/metabolism
MH  - Gene Expression
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Mice
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Plasminogen Activator Inhibitor 1/metabolism
MH  - S Phase/physiology
MH  - Tumor Cells, Cultured
MH  - alpha-Defensins/genetics/*metabolism
PMC - PMC8692109
OTO - NOTNLM
OT  - Colon cancer
OT  - EGF
OT  - EGFR
OT  - defensin6
OT  - migration
OT  - progression
OT  - serpine-1
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2022/01/04 06:00
MHDA- 2022/03/24 06:00
PMCR- 2022/01/01
CRDT- 2022/01/03 05:34
PHST- 2021/07/12 00:00 [received]
PHST- 2021/11/02 00:00 [accepted]
PHST- 2022/01/03 05:34 [entrez]
PHST- 2022/01/04 06:00 [pubmed]
PHST- 2022/03/24 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - ijmsv19p0034 [pii]
AID - 10.7150/ijms.64850 [doi]
PST - epublish
SO  - Int J Med Sci. 2022 Jan 1;19(1):34-46. doi: 10.7150/ijms.64850. eCollection 2022.