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SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice II

ABSTRACT: Characterization of the effects of Sox2 heterozygosity on tumorigenesis in p27-/- pituitary tumors.

ORGANISM(S): Mus musculus

PROVIDER: GSE152008 | GEO | 2021/02/24

REPOSITORIES: GEO

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SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice I

Project description:Characterization of the initiation and development of pituitary intermediate lobe tumors in p27-/- mice.

2021-02-24 | GSE152007 | GEO

SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice

Project description:SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice

| PRJNA638090 | ENA

SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-02-24 | GSE152010 | GEO

SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice I

Project description:SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice I

| PRJNA638092 | ENA

SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice II

Project description:SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice II

| PRJNA638093 | ENA

SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice III

Project description:SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice III

| PRJNA638094 | ENA

SOX2 is required independently in both stem and differentiated cells for pituitary tumor genesis in p27 null mice III

Project description:Exploration of the molecular mechanisms underlying melanotroph tumourigenesis and the role of SOX2 in both SCs and melanotrophs

2021-02-24 | GSE152009 | GEO

SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis in <i>p27</i>-null mice.

Project description:P27, a cell cycle inhibitor, is also able to drive repression of Sox2 This interaction plays a crucial role during development of p27-/- pituitary tumors because loss of one copy of Sox2 impairs tumorigenesis [H. Li et al., Cell Stem Cell 11, 845-852 (2012)]. However, SOX2 is expressed in both endocrine and stem cells (SCs), and its contribution to tumorigenesis in either cell type is unknown. We have thus explored the cellular origin and mechanisms underlying endocrine tumorigenesis in p27-/- pituitaries. We found that pituitary hyperplasia is associated with reduced cellular differentiation, in parallel with increased levels of SOX2 in stem and endocrine cells. Using conditional loss-of-function and lineage tracing approaches, we show that SOX2 is required cell autonomously in p27-/- endocrine cells for these to give rise to tumors, and in SCs for promotion of tumorigenesis. This is supported by studies deleting the Sox2 regulatory region 2 (Srr2), the target of P27 repressive action. Single cell transcriptomic analysis further reveals that activation of a SOX2-dependent MAPK pathway in SCs is important for tumorigenesis. Altogether, our data highlight different aspects of the role of SOX2 following loss of p27, according to cellular context, and uncover an unexpected SOX2-dependent tumor-promoting role for SCs. Our results imply that targeting SCs, in addition to tumor cells, may represent an efficient antitumoral strategy in certain contexts.

| S-EPMC7896314 | biostudies-literature

p27-affinity-purified mass spectrometry anslysis

Project description:This project aims to identify p27 modification sites.

2023-01-05 | PXD039223 | Pride

Cisplatin induces the rearrangement of RBPs on CDKN1B/p27 mRNA

Project description:Cisplatin (CP) is a chemotherapeutic drug that is used to cure different types of cancer. CP induces DNA damage and leads to cell cycle arrest. The cyclin-dependent kinase inhibitor 1B (CDKN1B), also termed p27, plays an important role in the drug response ; and increased levels of p27 correlated with CP resistance. In HEK293 cells, we observed that p27 mRNAs levels increased whereas protein level drastically decreased in cells treated with CP; suggesting post-transcriptional regulatory events. To further understand the underlying mechanisms, we applied a biochemical approach combined with mass-spectrometry to systematically identify the RNA-binding proteins (RBPs) that are bound to the 3’UTR of p27 mRNAs in CP-treated versus non-treated cells in vivo. We found that 24 proteins, most of them known RBPs such HuR, hNRNPD, changed their association with p27 mRNA upon CP treatement. Furthermore, knock-down of a subset of the identified RBPs led to the inhibition of the CP-induced increase of p27 mRNA levels. In conclusion, these results highlight substantial rearrangement between RBPs and p27 mRNA upon CP treatment and corroborate the importance of post-transcriptional control in cellular drug response.

2019-09-27 | PXD008498 | Pride

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