Proteomics

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Trib3 modulates PPAR-mediated growth inhibition by interfering with the MLL complex in breast cancer cells


ABSTRACT: Dysregulation of pathways due to mutations on oncogenes or tumor suppressors that leads to aberrant expression or activity of proteins is the most well understood mechanism that drives cancer initiation and progression. TRIB3, a member of the Tribbles family of pseudokinases, is often found dysregulated in cancer and has been associated with breast cancer initiation and metastasis formation. However, the underlying mechanisms by which TRIB3 contributes to these events are far from being understood. In contrast PPAR, a well-known transcription factor that belongs to the superfamily of nuclear receptors, has gained attention in recent years as drug target in breast cancer. PPAR possess anti-proliferative abilities and inducing its expression has been shown beneficial in different cancer models. In this study, we demonstrated that TRIB3 regulates PPAR expression in breast cancer cells and that TRIB3 interacts with the WRAD complex in these cells. We showed that TRIB3 expression influence H3K4me3 levels genome wide and specifically at the PPARG locus. All in all, our study situates TRIB3 as a new epigenetic regulator and represents a new line of research for the Tribbles scientific community, opening the door for future targeted therapeutic interventions for breast cancer patients

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Harmjan Vos  

LAB HEAD: Eric Kalkhoven

PROVIDER: PXD036341 | Pride | 2022-10-13

REPOSITORIES: Pride

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Publications

TRIB3 Modulates PPARγ-Mediated Growth Inhibition by Interfering with the MLL Complex in Breast Cancer Cells.

Hernández-Quiles Miguel M   Baak Rosalie R   Orea-Soufi Alba A   Borgman Anouska A   den Haan Suzanne S   Sobrevals Alcaraz Paula P   Jongejan Aldo A   van Es Robert R   Velasco Guillermo G   Vos Harmjan H   Kalkhoven Eric E  

International journal of molecular sciences 20220911 18


Aberrant expression or activity of proteins are amongst the best understood mechanisms that can drive cancer initiation and progression, as well as therapy resistance. TRIB3, a member of the Tribbles family of pseudokinases, is often dysregulated in cancer and has been associated with breast cancer initiation and metastasis formation. However, the underlying mechanisms by which TRIB3 contributes to these events are unclear. In this study, we demonstrate that TRIB3 regulates the expression of PPA  ...[more]

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