Adipocytes fuel gastric cancer omental metastasis via PITPNC1-mediated fatty acid metabolic reprogramming
| Autor: | Wangjun Liao, Dongping Chen, Kelin Lin, Bishan Liang, Yujing Tan, Yanxiao Liang, Jiazhu Hu, Shuyi Zhang, Qiong Huang, Qijing Wu, Jingyu Li, Wanming He, Xingbin Hu, Min Shi, Yang Zhao, Jin Wang, Hao Wang, Zhiqi Yao, Yajing Liu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
CD36 Antigens
0301 basic medicine Cell Survival PITPNC1 CD36 Gene Expression Mice Nude Medicine (miscellaneous) Adenocarcinoma Biology Metastasis 03 medical and health sciences chemistry.chemical_compound Stomach Neoplasms In vivo Cell Line Tumor Adipocytes medicine Animals Humans Gene silencing Gene Silencing omental metastasis anoikis resistance Pharmacology Toxicology and Pharmaceutics (miscellaneous) Beta oxidation fatty acid oxidation Peritoneal Neoplasms Carnitine O-Palmitoyltransferase Fatty acid metabolism gastric cancer Fatty Acids Membrane Transport Proteins Cancer Models Theoretical Anoikis medicine.disease Immunohistochemistry Coculture Techniques Up-Regulation Disease Models Animal 030104 developmental biology chemistry Cancer research biology.protein Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.28219 |
| Popis: | Omental metastasis occurs frequently in gastric cancer (GC) and is considered one of the major causes of gastric cancer-related mortality. Recent research indicated that omental adipocytes might mediate this metastatic predilection. Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) was identified to have a crucial role in metastasis. However, whether PITPNC1 participates in the interaction between adipocytes and GC omental metastasis is unclear. Methods: We profiled and analyzed the expression of PITPNC1 through analysis of the TCGA database as well as immunohistochemistry staining using matched GC tissues, adjacent normal gastric mucosa tissues (ANTs), and omental metastatic tissues. The regulation of PITPNC1 by adipocytes was explored by co-culture systems. By using both PITPNC1 overexpression and silencing methods, the role of PITPNC1 in anoikis resistance and metastasis was determined through in vitro and in vivo experiments. Results: PITPNC1 was expressed at higher rates in GC tissues than in ANTs; notably, it was higher in omental metastatic lesions. Elevated expression of PITPNC1 predicted higher rates of omental metastasis and a poor prognosis. PITPNC1 promoted anoikis resistance through fatty acid metabolism by upregulating CD36 and CPT1B expression. Further, PITPNC1 was elevated by adipocytes and facilitated GC omental metastasis. Lastly, in vivo studies showed that PITPNC1 was a therapeutic indicator of fatty acid oxidation (FAO) inhibition. Conclusion: Elevated expression of PITPNC1 in GC is correlated with an advanced clinical stage and a poor prognosis. PITPNC1 promotes anoikis resistance through enhanced FAO, which is regulated by omental adipocytes and consequently facilitates GC omental metastasis. Targeting PITPNC1 might present a promising strategy to treat omental metastasis. |
| Databáze: | OpenAIRE |
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