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Series GSE243320 Query DataSets for GSE243320
Status Public on Oct 01, 2023
Title RSK3 switches cell fate: from stress-induced senescence to malignant progression
Organism Homo sapiens
Experiment type Expression profiling by array
Summary TGFβ signaling induces several cell phenotypes including cellular senescence, a stable form of cell cycle arrest accompanied by a secretory program, and epithelial-mesenchymal transition (EMT) in normal epithelial cells. During carcinogenesis cells lose the ability to undergo senescence in response to TGFβ but they maintain an EMT, which can contribute to tumor progression and resistance. A screen with active kinases in HMECs upon TGFβ treatment identified that the serine threonine kinase RSK3, or RPS6KA2, reverted TGFβ-induced senescence. Interestingly, RSK3 expression decreased in response to TGFβ in a SMAD3-dependent manner, and its constitutive expression rescued SMAD3-induced premature senescence, indicating that decrease of RSK3 itself contributes to TGFβ-induced senescence. Mechanistically, using transcriptomic analyses and affinity purification coupled to mass spectrometry-based proteomics, we unveiled that RSK3 regulates senescence by inhibiting NF-κΒ pathway through the decrease in proteasome-mediated IκBα degradation. Strikingly, senescent TGFβ-treated HMEC display features of epithelial to mesenchymal transition (EMT) and during RSK3-induced senescence escape HMEC conserve EMT features. Importantly, RSK3 expression correlates with EMT and invasion, and anti-correlates with senescence and NF-κΒ in human claudin-low breast tumors and its expression accelerates formation of breast invasive tumors in the mouse mammary gland. We conclude that RSK3 switches cell fate from senescence to malignancy in response to TGFβ signals.
Overall design hTERT-immortalized Human Mammary Epithelial Cells (HMECT) were transduced with either pWZL control or pWZL encoding RSK3 vectors and treated or not with TGFb. Three independent experiments have been performed.
Contributor(s) Flaman J, Huna A, Bernard D
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Submission date Sep 15, 2023
Last update date Oct 02, 2023
Contact name jean-michel flaman
Phone +33687477812
Organization name Inserm 1052
Department CRCL
Street address 28 rue Laennec
City Lyon
ZIP/Postal code 69373
Country France
Platforms (1)
GPL13497 Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version)
Samples (9)
GSM7783272 NT_R1
GSM7783273 NT_R2
GSM7783274 NT_R3
BioProject PRJNA1017821

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Supplementary file Size Download File type/resource
GSE243320_RAW.tar 19.4 Mb (http)(custom) TAR (of TXT)

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