Home Blog of Signal Transduction Epigenetics Epigenetic Reader Domain Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation

Hepatocellular carcinoma (HCC) is the most common type of primary liver malignancy with poor prognosis worldwide. Emerging evidences demonstrated critical roles of lipid de novo synthesis in HCC progression, yet its regulatory mechanisms are not fully understood. Herein, we found that tuftelin 1 (TUFT1), an acidic phosphorylated glycoprotein with secretory capacity, was significantly upregulated in HCC and had an excellent correlation with patient survival and malignancy features. Through database mining and experimental validation, we found that TUFT1 was associated with fatty acid metabolism and promoted lipid accumulation in HCC cells. Further, we found that TUFT1 can interact with CREB1, a transcription factor for hepatic lipid metabolism, and regulate its activity and the transcriptions of key enzymes for lipogenesis. TUFT1 promoted HCC cell proliferation significantly, which was partially reversed by treatment of an inhibitor of CREB1, KG-501. Moreover, TUFT1 promoted the capacity of HCC cell invasion in vitro, which was likely mediated by its association with zyxin, a zinc-binding phosphoprotein responsible for the formation of fully mature focal adhesions on extracellular matrix. We found that TUFT1 can interact with ZYX and inhibit its expression and recruitments to focal complexes in HCC cells. Collectively, our study uncovered new regulatory mechanisms of TUFT1-mediated lipogenesis, cell proliferation, and invasion.

 

Comments:

Your research findings on TUFT1 in hepatocellular carcinoma (HCC) are fascinating! It seems TUFT1 plays a pivotal role in HCC progression by impacting lipid metabolism, cell proliferation, and invasion.

TUFT1's upregulation in HCC, its correlation with patient survival and malignancy features, and its association with fatty acid metabolism indicate its significance in the disease. The interaction between TUFT1 and CREB1, a key transcription factor for hepatic lipid metabolism, sheds light on TUFT1's role in regulating lipogenesis. Additionally, its influence on the transcription of key enzymes involved in lipogenesis further establishes its impact.

The observed promotion of HCC cell proliferation by TUFT1, which can be partially reversed by a CREB1 inhibitor, KG-501, strengthens the link between TUFT1 and CREB1-mediated pathways in HCC progression. Furthermore, TUFT1's association with zyxin and its inhibition of zyxin expression and recruitment to focal complexes in HCC cells suggests a mechanism for TUFT1-mediated HCC cell invasion.

Your study has unveiled novel insights into TUFT1's regulatory mechanisms in HCC, shedding light on its involvement in lipid metabolism, cell proliferation, and invasion. This research may pave the way for potential therapeutic strategies targeting TUFT1 or its associated pathways to combat HCC.

Related Products

Cat.No. Product Name Information
S8409 KG-501 KG-501 is a cAMP response element-binding protein (CREB) inhibitor that disrupts CREB-dependent transcription (Ki = 10 μM) and CREB:CBP interaction (Ki = 50 μM). It also disrupts phospho (Ser-133) CREB binding to KIX with a Ki of ≈90 μM, using concentrations of CREB that were within the linear range of the binding assay.

Related Targets

Epigenetic Reader Domain