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Peer-reviewedCC BYInternational journal of molecular sciences

Bacteroides fragilis Toxin Induces Extracellular Domain Cleavage of HER2 in Intestinal Epithelial Cells.

  • Sang-Hyeon Yoo1
  • Ha-Neul Jang1
  • Da-Hye Kang1,2
  • Ju-Eun Hong1,3
  • Jiyun Hong1
  • Young Woo Eom4
  • Ki-Jong Rhee1
4 affiliations
  1. 1Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Republic of Korea.
  2. 2Department of Obstetrics, Gynecology & Women's Health, University of Missouri School of Medicine, Columbia, MO 65211, USA.
  3. 3Medical Device Business Division, ECO DM LAB Co., Ltd., Cheongju 28121, Republic of Korea.
  4. 4Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea.
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Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) secretes Bacteroides fragilis toxin (BFT), a metalloprotease that disrupts intestinal epithelial integrity and activates pro-inflammatory signaling. Although E-cadherin cleavage is a well-established response to BFT, the involvement of other membrane receptors in BFT-induced signaling remains poorly defined. In this study, we examined whether HER2 undergoes proteolytic processing following BFT exposure and whether HER2 contributes to BFT-induced ERK activation. In HT29/c1 and MCF-7 epithelial cells, BFT induced the loss of full-length 185 kDa HER2 and the generation of a membrane-tethered ~95 kDa fragment. This truncated HER2 underwent γ-secretase-dependent intramembrane processing and subsequent proteasomal degradation. Knockdown of MMP-7 or ADAM10 did not prevent HER2 cleavage, indicating that neither protease is required for this process. In addition, BFT-induced ERK phosphorylation was observed in HER2-expressing cells but was abolished in HER2-deficient HT29/c1 clones, whereas E-cadherin cleavage and IL-8 secretion remained detectable. These findings identify HER2 as a previously unrecognized target of BFT-induced proteolytic remodeling and support a contribution of HER2 to BFT-induced ERK activation.

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Cite

BibTeXRIS
BibTeX
@article{yoo2026bacteroides,
  title = {{Bacteroides fragilis Toxin Induces Extracellular Domain Cleavage of HER2 in Intestinal Epithelial Cells.}},
  author = {Sang-Hyeon Yoo and Ha-Neul Jang and Da-Hye Kang and Ju-Eun Hong and Jiyun Hong and Young Woo Eom and Ki-Jong Rhee},
  journal = {International journal of molecular sciences},
  year = {2026},
  month = sep,
  doi = {10.3390/ijms27198497},
  url = {https://europepmc.org/article/MED/42883746},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Bacteroides fragilis Toxin Induces Extracellular Domain Cleavage of HER2 in Intestinal Epithelial Cells.
AU  - Sang-Hyeon Yoo
AU  - Ha-Neul Jang
AU  - Da-Hye Kang
AU  - Ju-Eun Hong
AU  - Jiyun Hong
AU  - Young Woo Eom
AU  - Ki-Jong Rhee
PY  - 2026
DA  - 2026/09/23
JO  - International journal of molecular sciences
DO  - 10.3390/ijms27198497
UR  - https://europepmc.org/article/MED/42883746
AB  - Enterotoxigenic Bacteroides fragilis (ETBF) secretes Bacteroides fragilis toxin (BFT), a metalloprotease that disrupts intestinal epithelial integrity and activates pro-inflammatory signaling. Although E-cadherin cleavage is a well-established response to BFT, the involvement of other membrane receptors in BFT-induced signaling remains poorly defined. In this study, we examined whether HER2 undergoes proteolytic processing following BFT exposure and whether HER2 contributes to BFT-induced ERK activation. In HT29/c1 and MCF-7 epithelial cells, BFT induced the loss of full-length 185 kDa HER2 and the generation of a membrane-tethered ~95 kDa fragment. This truncated HER2 underwent γ-secretase-dependent intramembrane processing and subsequent proteasomal degradation. Knockdown of MMP-7 or ADAM10 did not prevent HER2 cleavage, indicating that neither protease is required for this process. In addition, BFT-induced ERK phosphorylation was observed in HER2-expressing cells but was abolished in HER2-deficient HT29/c1 clones, whereas E-cadherin cleavage and IL-8 secretion remained detectable. These findings identify HER2 as a previously unrecognized target of BFT-induced proteolytic remodeling and support a contribution of HER2 to BFT-induced ERK activation.
SN  - 1422-0067
ER  -