Acquired TRAIL Resistance Promotes Cancer Stemness and Malignant Behavior through CD44-SPHK1-STAT3 Signaling in Colorectal Cancer
, CD44⁺ HCT116-TR cells induced extensive lung metastasis with elevated CD44, p-SPHK1, and p-STAT3 expression, whereas CD44-deficient mice injected with TRAIL-resistant CMT-93 cells showed minimal metastatic burden and reduced pathway activation, confirming the essential role of CD44 in TRAIL-associated metastasis. TCGA colon cancer analysis further revealed CD44 overexpression in tumors and its association with poor overall survival. Collectively, these findings show that acquired TRAIL resistance promotes CD44-mediated CSC expansion and metastatic potential through SPHK1/STAT3 activation, highlighting CD44 as a key therapeutic target in CRC.
Authors
- Byung Chul Jin (ORCID: https://orcid.org/0000-0002-0651-7487)
- Seung Young Seo (ORCID: https://orcid.org/0000-0003-2018-0013)
- Sang WooK Kim
- Se Lim Kim
Institutions
- Jeonbuk National University Hospital (KR)
- Jeonbuk National University (KR)
Publication Details
- Journal
- Biomolecules & Therapeutics
- Published
- 2026-10-29
- DOI
- https://doi.org/10.4062/biomolther.2026.083
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Biomedical Research Institute, Jeonbuk National University Hospital
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- Jeonbuk National University