A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma

Saiful Effendi Syafruddin, Paulo Rodrigues, Erika Vojtasova, Saroor A. Patel, M. Nazhif Zaini, Johanna Burge, Anne Y. Warren, Grant D. Stewart, Tim Eisen, Dóra Bihary, Shamith A. Samarajiwa, Sakari Vanharanta

Research output: Contribution to journalArticle

Abstract

Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.

Original languageEnglish
Article number1152
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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Kruppel-Like Transcription Factors
homeostasis
Gene Regulatory Networks
Renal Cell Carcinoma
lipids
Tumors
Homeostasis
tumors
cancer
Carcinoma
Kidney
Lipids
Lipid Metabolism
lipid metabolism
Growth
Proto-Oncogene Proteins c-sis
Neoplasms
Zinc Fingers
Metabolic Networks and Pathways
cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma. / Syafruddin, Saiful Effendi; Rodrigues, Paulo; Vojtasova, Erika; Patel, Saroor A.; Zaini, M. Nazhif; Burge, Johanna; Warren, Anne Y.; Stewart, Grant D.; Eisen, Tim; Bihary, Dóra; Samarajiwa, Shamith A.; Vanharanta, Sakari.

In: Nature Communications, Vol. 10, No. 1, 1152, 01.12.2019.

Research output: Contribution to journalArticle

Syafruddin, SE, Rodrigues, P, Vojtasova, E, Patel, SA, Zaini, MN, Burge, J, Warren, AY, Stewart, GD, Eisen, T, Bihary, D, Samarajiwa, SA & Vanharanta, S 2019, 'A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma', Nature Communications, vol. 10, no. 1, 1152. https://doi.org/10.1038/s41467-019-09116-x
Syafruddin, Saiful Effendi ; Rodrigues, Paulo ; Vojtasova, Erika ; Patel, Saroor A. ; Zaini, M. Nazhif ; Burge, Johanna ; Warren, Anne Y. ; Stewart, Grant D. ; Eisen, Tim ; Bihary, Dóra ; Samarajiwa, Shamith A. ; Vanharanta, Sakari. / A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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