Int J Med Sci 2022; 19(1):34-46. doi:10.7150/ijms.64850 This issue

Research Paper

Human α-defensin 6 (HD6) suppresses CRC proliferation and metastasis through abolished EGF/EGFR signaling pathway

Po-Li Wei1,2,3,4*, Jang-Chun Lin5,6*, Chin-Sheng Hung2, Precious Takondwa Makondi7, Uyanga Batzorig2, Tung-Cheng Chang2,8,9, Chien-Yu Huang2,8,9, Yu-Jia Chang10,11,12✉

1. Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
2. Department of Surgery, College of Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
3. Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
4. Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
5. Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
6. Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
7. Kamuzu Central Hospital - National Cancer Center, Lilongwe, Malawi.
8. Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
9. Division of Colon and Rectal, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
10. Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
11. Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
12. Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
* These authors contributed equally.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Wei PL, Lin JC, Hung CS, Makondi PT, Batzorig U, Chang TC, Huang CY, Chang YJ. Human α-defensin 6 (HD6) suppresses CRC proliferation and metastasis through abolished EGF/EGFR signaling pathway. Int J Med Sci 2022; 19(1):34-46. doi:10.7150/ijms.64850. Available from https://www.medsci.org/v19p0034.htm

File import instruction

Abstract

Graphic abstract

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 α-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.

Keywords: Colon cancer, defensin6, progression, migration, serpine-1, EGF, EGFR