TM4SF5 overexpressed in hepatocellular carcinoma activates focal adhesion kinase (FAK) during tumor cell migration. However, it remains unknown how TM4SF5 in hepatocellular carcinoma cells compromises with immune actions initiated by extracellular cytokines. Normal and cancerous hepatocytes with or without TM4SF5 expression were analyzed for the effects of cytokine signaling activity on TM4SF5/FAK signaling and metastatic potential. We found that interleukin-6 (IL-6) was differentially expressed in hepatocytes depending on cancerous malignancy and TM4SF5 expression. IL-6 treatment activated FAK and STAT3 and enhanced focal adhesion (FA) formation in TM4SF5-null cells, but it decreased TM4SF5-dependent FAK activity and FA formation in SNU761-TM4SF5 cells. STAT3 suppression abolished the IL-6-mediated effects in normal Chang cells, but it did not recover the TM4SF5-dependent FAK activity that was inhibited by IL-6 treatment in cancerous SNU761-TM4SF5 cells. In addition, modulation of FAK activity did not change the IL-6-mediated STAT3 activity in either the Chang or SNU761 cell system. TM4SF5 expression in SNU761 cells caused invasive extracellular matrix degradation negatively depending on IL-6/IL-6 receptor (IL-6R) signaling. Thus, it is likely that hepatic cancer cells adopt TM4SF5-dependent FAK activation and metastatic potential by lowering IL-6 expression and avoiding its immunological action through the IL-6-STAT3 pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135608 | PMC |
| http://dx.doi.org/10.1128/MCB.00660-14 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Association between hepatocyte TM4SF5 expression and gut microbiome dysbiosis during non-alcoholic fatty liver disease development.
Life Sci
December 2024
Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:
Gut microbiome dysbiosis is involved in non-alcoholic fatty liver disease (NAFLD) development. Hepatic transmembrane 4 L six family member 5 (TM4SF5) overexpression promotes NAFLD. However, how gut microbiota are associated with TM4SF5-mediated NAFLD remains unexplored.
View Article and Find Full Text PDFInnovative Therapeutic Delivery of Metastasis-Associated in Colon Cancer 1-Suppressing miRNA Using High Transmembrane 4 L6 Family Member 5-Targeting Exosomes in Colorectal Cancer Mouse Models.
Int J Mol Sci
August 2024
Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Elevated metastasis-associated in colon cancer 1 (MACC1) expression in colorectal cancer patients, and high transmembrane 4 L6 family member 5 (TM4SF5) protein expressed on various solid tumors' surface, are linked to aggressive cancer behavior and progression. In this study, adipose-derived stem cells (ASCs) were engineered to produce exosomes (Ex) that target the TM4SF5 protein on tumors. Moreover, MACC1-targeting microRNA was encapsulated within the Ex, resulting in TM4SF5-targeting Ex (MACC1-suppressing miRNA; miR-143).
View Article and Find Full Text PDFFIGNL1 Promotes Hepatocellular Carcinoma Formation Remodeling ECM-receptor Interaction Pathway Mediated by HMMR.
Curr Gene Ther
April 2024
Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Department of Hepatobiliary Surgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, China.
Background: The development of novel biomarkers is crucial for the treatment of HCC. In this study, we investigated a new molecular therapeutic target for HCC. Fidgetin-like 1 (FIGNL1) has been reported to play a vital role in lung adenocarcinoma.
View Article and Find Full Text PDFTM4SF5-mediated abnormal food-intake behavior and apelin expression facilitate non-alcoholic fatty liver disease features.
iScience
September 2023
Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
Transmembrane 4 L six family member 5 (TM4SF5) engages in non-alcoholic steatohepatitis (NASH), although its mechanistic roles are unclear. Genetically engineered mice fed normal chow or high-fat diet for either an entire day or a daytime-feeding (DF) pattern were analyzed for metabolic parameters. Compared to wild-type and knockout mice, hepatocyte-specific TM4SF5-overexpressing -TG (TG) mice showed abnormal food-intake behavior during the mouse-inactive daytime, increased apelin expression, increased food intake, and higher levels of NASH features.
View Article and Find Full Text PDFThree Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance.
Pharmaceuticals (Basel)
January 2023
Department of Biomedical Science and Therapeutics, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia.
There are six members of the transmembrane 4 superfamily (TM4SF) that have similar topology and sequence homology. Physiologically, they regulate tissue differentiation, signal transduction pathways, cellular activation, proliferation, motility, adhesion, and angiogenesis. Accumulating evidence has demonstrated, among six TM4SF members, the regulatory roles of transmembrane 4 L6 domain family members, particularly TM4SF1, TM4SF4, and TM4SF5, in cancer angiogenesis, progression, and chemoresistance.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!