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Pharmacological Inhibition or Silencing of TREM1 Restrains HCC Cell Metastasis by Inactivating TLR/PI3K/AKT Signaling.
Ren, Ling; Qiao, Guang-Lei; Zhang, Shu-Xian; Zhang, Zhi-Mei; Lv, Sheng-Xiang.
Afiliación
  • Ren L; Department of Gastroenterology, The Affifiliated Lianyungang Hospital of Xuzhou Medical University, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
  • Qiao GL; Department of Gastroenterology, The Affiliated Hospital of Kangda College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
  • Zhang SX; Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang ZM; Department of Gastroenterology, The Affifiliated Lianyungang Hospital of Xuzhou Medical University, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
  • Lv SX; Department of Gastroenterology, The Affiliated Hospital of Kangda College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
Cell Biochem Biophys ; 2024 Jul 02.
Article en En | MEDLINE | ID: mdl-38954352
ABSTRACT
Hepatocellular carcinoma (HCC), a widely prevalent malignancy strongly linked to inflammation, remains a significant public health concern. Triggering receptor expressed on myeloid cells 1 (TREM1), a modulator of inflammatory responses identified in recent years, has emerged as a crucial facilitator in cancer progression. Despite its significance, the precise regulatory mechanism of TREM1 in HCC metastasis remains unanswered. In the present investigation, we observed aberrant upregulation of TREM1 in HCC tissues, which was significantly linked to poorer overall survival. Inhibition of TREM1 expression resulted in a significant reduction in HCC Huh-7 and MHCC-97H cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) process. Furthermore, inhibiting TREM1 decreased protein expressions of toll-like receptor 2/4 (TLR2/4) and major myeloid differentiation response gene 88 (MyD88), leading to the inactivation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in HCC cells. Notably, these effects were reversed by treatment with TLR2-specific agonist (CU-T12-9), indicating a potential crosstalk between TREM1 and TLR2/4. Mechanistic studies revealed a direct interaction between TREM1 and both TLR2 and TLR4. In vivo studies demonstrated that inhibition of TREM1 suppressed the growth of HCC cells in the orthotopic implant model and its metastatic potential in the experimental lung metastasis model. Overall, our findings underscore the role of TREM1 inhibition in regulating EMT and metastasis of HCC cells by inactivating the TLR/PI3K/AKT signaling pathway, thereby providing deeper mechanistic insights into how TREM1 regulates metastasis during HCC progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Biochem Biophys Asunto de la revista: BIOFISICA / BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Biochem Biophys Asunto de la revista: BIOFISICA / BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos