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 (TU...

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Main Authors: Lei Zhu, Kai X. Zhou, Ming Z. Ma, Lin L. Yao, Yan L. Zhang, Hui Li, Chang Du, Xiao M. Yang
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2022/1590717
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author Lei Zhu
Kai X. Zhou
Ming Z. Ma
Lin L. Yao
Yan L. Zhang
Hui Li
Chang Du
Xiao M. Yang
author_facet Lei Zhu
Kai X. Zhou
Ming Z. Ma
Lin L. Yao
Yan L. Zhang
Hui Li
Chang Du
Xiao M. Yang
author_sort Lei Zhu
collection DOAJ
description 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.
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spelling doaj-art-ba5d7c909e384e0393473e3f2460ea692025-02-03T01:07:31ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/1590717Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion MaturationLei Zhu0Kai X. Zhou1Ming Z. Ma2Lin L. Yao3Yan L. Zhang4Hui Li5Chang Du6Xiao M. Yang7State Key Laboratory of Oncogenes and Related GenesState Key Laboratory of Oncogenes and Related GenesDepartment of Infectious DiseasesState Key Laboratory of Oncogenes and Related GenesState Key Laboratory of Oncogenes and Related GenesState Key Laboratory of Oncogenes and Related GenesState Key Laboratory of Oncogenes and Related GenesState Key Laboratory of Oncogenes and Related GenesHepatocellular 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.http://dx.doi.org/10.1155/2022/1590717
spellingShingle Lei Zhu
Kai X. Zhou
Ming Z. Ma
Lin L. Yao
Yan L. Zhang
Hui Li
Chang Du
Xiao M. Yang
Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation
Journal of Immunology Research
title Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation
title_full Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation
title_fullStr Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation
title_full_unstemmed Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation
title_short Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation
title_sort tuftelin 1 facilitates hepatocellular carcinoma progression through regulation of lipogenesis and focal adhesion maturation
url http://dx.doi.org/10.1155/2022/1590717
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