A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Nature communications - 10(2019), 1 vom: 11. März, Seite 1152 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Syafruddin, Saiful E [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 05.04.2019 Date Revised 04.12.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-019-09116-x |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM294818812 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM294818812 | ||
| 003 | DE-627 | ||
| 005 | 20231225082318.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-019-09116-x |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0982.xml |
| 035 | |a (DE-627)NLM294818812 | ||
| 035 | |a (NLM)30858363 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Syafruddin, Saiful E |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 05.04.2019 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a KLF6 protein, human |2 NLM | |
| 650 | 7 | |a Kruppel-Like Factor 6 |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-sis |2 NLM | |
| 650 | 7 | |a SREBF1 protein, human |2 NLM | |
| 650 | 7 | |a SREBF2 protein, human |2 NLM | |
| 650 | 7 | |a Sterol Regulatory Element Binding Protein 1 |2 NLM | |
| 650 | 7 | |a Sterol Regulatory Element Binding Protein 2 |2 NLM | |
| 650 | 7 | |a MTOR protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.1.1 |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Rodrigues, Paulo |e verfasserin |4 aut | |
| 700 | 1 | |a Vojtasova, Erika |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Saroor A |e verfasserin |4 aut | |
| 700 | 1 | |a Zaini, M Nazhif |e verfasserin |4 aut | |
| 700 | 1 | |a Burge, Johanna |e verfasserin |4 aut | |
| 700 | 1 | |a Warren, Anne Y |e verfasserin |4 aut | |
| 700 | 1 | |a Stewart, Grant D |e verfasserin |4 aut | |
| 700 | 1 | |a Eisen, Tim |e verfasserin |4 aut | |
| 700 | 1 | |a Bihary, Dóra |e verfasserin |4 aut | |
| 700 | 1 | |a Samarajiwa, Shamith A |e verfasserin |4 aut | |
| 700 | 1 | |a Vanharanta, Sakari |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 10(2019), 1 vom: 11. März, Seite 1152 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2019 |g number:1 |g day:11 |g month:03 |g pages:1152 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-019-09116-x |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2019 |e 1 |b 11 |c 03 |h 1152 | ||