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Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers [RNA-seq]

ABSTRACT: Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers [RNA-seq]

PROVIDER: PRJNA993666 | ENA |

REPOSITORIES: ENA

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Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers [RNA-seq]

Project description:In lung and prostate adenocarcinomas, neuroendocrine (NE) transformation to an aggressive derivative resembling small cell lung cancer (SCLC) is associated with poor prognosis. We previously described dependency of SCLC on the nuclear transporter exportin 1. Here we explored the role of exportin 1 in NE transformation. We observed upregulated exportin 1 in lung and prostate pre-transformation adenocarcinomas. Exportin 1 was induced upregulated following genetic inactivation of TP53 and RB1 in lung and prostate adenocarcinoma cell lines, accompanied by increased sensitivity to the exportin 1 inhibitor selinexor in vitro. Exportin 1 inhibition prevented NE transformation and extended response to targeted therapies in both lung anddifferent TP53/RB1-inactivated prostate adenocarcinoma xenograft models that acquire NE features upon treatment with the AR inhibitor enzalutamide, and extended response to the EGFR inhibitor osimertinib in a lung cancer transformation patient-derived xenograft (PDX) model exhibiting combined adenocarcinoma/SCLC histology. Ectopic SOX2 expression restored the enzalutamide-promoted NE transformationNE phenotype on adenocarcinoma-to-NE transformation xenograft models despite selinexor treatment. Selinexor sensitized NE-transformed lung and prostate small cell carcinoma PDXs tumors after NE transformation to standard cytotoxics. Together these data nominate exportin 1 inhibition as a novel potential therapeutic approach target to constrain lineage plasticity and prevent or treat NE transformation in lung and prostate adenocarcinoma.

2023-07-12 | GSE237072 | GEO

Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers [ATAC-seq]

2023-07-12 | GSE237071 | GEO

Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers

Project description:Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers

| PRJNA993668 | ENA

Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers [ATAC-seq]

Project description:Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers [ATAC-seq]

| PRJNA993665 | ENA

Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 downregulation in lung and prostate cancers

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

2023-07-12 | GSE237074 | GEO

Exportin 1 inhibition prevents neuroendocrine transformation through SOX2 down-regulation in lung and prostate cancers.

Project description:In lung and prostate adenocarcinomas, neuroendocrine (NE) transformation to an aggressive derivative resembling small cell lung cancer (SCLC) is associated with poor prognosis. We previously described dependency of SCLC on the nuclear transporter exportin 1. Here, we explored the role of exportin 1 in NE transformation. We observed up-regulated exportin 1 in lung and prostate pretransformation adenocarcinomas. Exportin 1 was up-regulated after genetic inactivation of TP53 and RB1 in lung and prostate adenocarcinoma cell lines, accompanied by increased sensitivity to the exportin 1 inhibitor selinexor in vitro. Exportin 1 inhibition prevented NE transformation in different TP53/RB1-inactivated prostate adenocarcinoma xenograft models that acquire NE features upon treatment with the aromatase inhibitor enzalutamide and extended response to the EGFR inhibitor osimertinib in a lung cancer transformation patient-derived xenograft (PDX) model exhibiting combined adenocarcinoma/SCLC histology. Ectopic SOX2 expression restored the enzalutamide-promoted NE phenotype on adenocarcinoma-to-NE transformation xenograft models despite selinexor treatment. Selinexor sensitized NE-transformed lung and prostate small cell carcinoma PDXs to standard cytotoxics. Together, these data nominate exportin 1 inhibition as a potential therapeutic target to constrain lineage plasticity and prevent or treat NE transformation in lung and prostate adenocarcinoma.

| S-EPMC10777207 | biostudies-literature

Effect of Exportin-5 expression on Mouse fibroblasts in cell cycle re-entry phase

Project description:To analyze the effect of Exportin-5 expression on the MEF cells in cell cycle re-entry phase, we have employed whole genome microarray expression profiling on the MEF cells in cell cycle re-entry phase with and without down regulation of Exportin-5 gene. Mouse MEF cells were transfected with 60nM of siRNA targeting either Exportin-5 or negative control, and incubated for 12 hours. After incubation, cells were starved with DMEM containing 0.2% FCS for 48 hours and re-fed with DMEM containing 20%FCS for 24 hours, along with second siRNA transfection. Two independant expreiments were preformed.

2013-01-01 | E-GEOD-25498 | biostudies-arrayexpress

Identification the Expression of Sox2 in Colorectal Cancer Tissues

Project description:Sox2 has been studied in several types of human solid tumors. The investigators found that Sox2 had higher expression level in colorectal cancer and metastatic tissues than normal tissues. So the investigators assumed that whether Sox2 plays an important role in the progression and migration of colon cancer.

| 2124687 | ecrin-mdr-crc

Effect of Exportin-5 expression on Mouse fibroblasts in cell cycle re-entry phase

2013-01-01 | GSE25498 | GEO

TRIB3 inhibition by palbociclib sensitizes prostate cancer to ferroptosis via SOX2-mediated SLC7A11 downregulation

Project description:TRIB3 inhibition by palbociclib sensitizes prostate cancer to ferroptosis via SOX2-mediated SLC7A11 downregulation

| PRJNA1142522 | ENA