journal article·2025-01Open access

Synthetic Retinoid Sulfarotene Selectively Inhibits Tumor‐Repopulating Cells of Intrahepatic Cholangiocarcinoma via Disrupting Cytoskeleton by P‐Selectin/PSGL1 N‐Glycosylation Blockage

Xiaojing Du, Zhuoran Qi, Sinuo Chen, Jinlan Wu, Ye Xu, Sunkuan Hu, Zhijie Yu, Jiayun Hou, Yuan Fang, Jinglin Xia, Xin Cao

Advanced Science· Volume 12· Issue 3

Abstract

Abstract Intrahepatic cholangiocarcinoma (ICC) is a highly lethal malignancy that currently lacks effective clinical treatments. Eliminating stem cell‐like cancer cells is an extremely promising but challenging strategy for treating ICC. A recently developed synthetic retinoid, sulfarotene, abrogates proliferation, and induces apoptosis of tumor‐repopulating cells (TRCs) that exhibit stem cell‐like properties, yet its effect and underlying mechanisms remain elusive in ICC. It is found that although 5‐fluorouracil, cisplatin, pemigatinib, and gemcitabine all inhibit ICC‐TRCs, sulfarotene demonstrates superior efficacy. Sulfarotene induces retinoic acid receptor alpha (RARɑ) translocation from the cytoplasm to the nucleus, suppressing P‐selectin expression at the transcriptional level. Moreover, it directly interacts with fucosyltransferase 8 (FUT8), inhibiting the core fucosylation of P‐selectin glycoprotein ligand 1 (PSGL1). These actions collectively inhibit ICC‐TRCs via destroying PSGL1‐regulated cytoskeleton. The findings provide a strategy of inhibiting P‐selectin/PSGL1 interaction and altering PSGL1 glycosylation pattern to compromise the cytoskeletal integrity and eliminate ICC‐TRCs.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Cholangiocarcinoma and Gallbladder Cancer Studies · Ubiquitin and proteasome pathways · Glycosylation and Glycoproteins Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Liver Cancer Institute Zhongshan Hospital Fudan University 180 Fenglin Road Shanghai 200032 China

Endoscopy Center Shanghai East Hospital Tongji University School of Medicine Shanghai 200120 China

Department of Pediatrics Jiading District Central Hospital Shanghai 201800 China

Department of Gastroenterology The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000 China

Key Laboratory of Diagnosis and Treatment of Severe Hepato‐Pancreatic Diseases of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000 China

Wenzhou Key Laboratory of Hematology The First Affiliated Hospital of Wenzhou Medical University Wenzhou 325000 China

Biomedical Research Center Zhongshan Hospital Institute of Clinical Science Fudan University Shanghai 200032 China

Department of Liver Surgery Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education) Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai 200032 China

Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation First Affiliated Hospital of Wenzhou Medical University Wenzhou 325035 China

Institute of Clinical Science Zhongshan Hospital Fudan University Shanghai 200032 China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China

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