SREBP1 promotes invasive phenotypes by upregulating CYR61/CTGF via the Hippo-YAP pathway

in Endocrine-Related Cancer
Authors:
Chi-Yu Kuo Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan

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Yuan-Ching Chang Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan

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Ming-Nan Chien Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan

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Jie-Yang Jhuang Department of Pathology, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan

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Yi-Chiung Hsu Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan

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Shih-Yuan Huang Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan

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Shih-Ping Cheng Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan
Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

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https://orcid.org/0000-0002-6301-5096

Correspondence should be addressed to S-P Cheng: surg.mmh@gmail.com
DOI:
https://doi.org/10.1530/ERC-21-0256
Volume/Issue:
Volume 29: Issue 2
Article Type:
Research Article
Page Range:
47–58
Online Publication Date:
13 Dec 2021
Copyright:
© Society for Endocrinology 2021
Collections:
Top-cited articles of 2023
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Aberrant lipid metabolism provides bioenergetic, biosynthetic, and redox supplies to cancer cells. Previous studies have reported differential lipid profiling in thyroid malignancies. Sterol regulatory element-binding protein 1 (SREBP1), encoded by the SREBF1 gene, is a master regulator of cellular lipid homeostasis. The clinical and functional significance of SREBP1 in thyroid cancer is not well understood. Here, we showed that SREBP1 expression is significantly upregulated in invasive thyroid cancer than in normal thyroid tissue or benign thyroid nodules. High tumoral SREBP1 expression was associated with extrathyroidal extension, advanced disease stage, and shorter disease-specific survival in patients with differentiated thyroid cancer. SREBP1 overexpression significantly increased the oxygen consumption rate, filopodia formation, and migratory and invasive capacities of thyroid cancer cells. Knockdown of SREBF1 or treatment with an SREBP1 activation inhibitor fatostatin had the opposite effect. RNA-Seq analysis showed that modulation of SREBP1 expression was accompanied by corresponding changes in the expression of epithelial–mesenchymal transition markers and CYR61/CTGF. SREBP1-facilitated cell invasion could be abrogated by treatment with a YAP inhibitor such as verteporfin or genetic silencing of CYR61 or CTGF. In summary, SREBP1 upregulation can be used as a prognostic indicator for thyroid cancer and SREBP1 overexpression is involved in cancer invasiveness, at least partly, through upregulation of CYR61/CTGF via the Hippo-YAP pathway.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© Society for Endocrinology 2021
Page(s):
12
Received Date:
13 Nov 2021
Accepted Date:
25 Nov 2021
Print Publication Date:
01 Feb 2022
Online Publication Date:
13 Dec 2021
Keywords:
SREBP1; invasion; thyroid cancer; lipid metabolism

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