Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis I
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PROVIDER: PRJNA675508 | ENA |
REPOSITORIES: ENA
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Project description:Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis
| PRJNA756301 | ENA
Project description:Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis III
| PRJNA756304 | ENA
Project description:Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis II
| PRJNA756305 | ENA
Project description:The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we find that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic biomarker. Correlating this observation, we demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determine that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies. The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, the authors characterise cancer-specific transposable element-driven transpochimeric gene transcripts and highlight the role of POU5F1B in CRC growth and metastasis.
| S-EPMC9392749 | biostudies-literature
Project description:Tumors occasionally express oncogenes via aberrant activation of transposable elements (TE), but a role for this process in oncogenesis was seldom demonstrated. Here, we identify expression of the hominid-restricted retrogene POU5F1B through aberrant activation of an endogenous retroviral promoter as a strong negative prognostic marker in colorectal cancer (CRC). We further determine that POU5F1B is membrane-enriched and interacts with ERBB2 and associated effectors, and fosters the proliferation and metastatic potential of CRC cells through intracellular signaling events and release of trans-acting molecules involved in cell growth, angiogenesis and cell adhesion. As POU5F1B is apparently non-essential and only lowly expressed in normal tissues, and as POU5F1B-containing TE-driven transcripts are detected in other tumors besides CRC, these data provide interesting leads for the development of cancer therapies.
2022-08-02 | GSE161083 | GEO
Project description:The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor, we found that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic CRC biomarker. Correlating this observation, we could demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determined that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.
2022-08-02 | GSE182466 | GEO
Project description:The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor, we found that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic CRC biomarker. Correlating this observation, we could demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determined that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.
2022-08-02 | GSE182465 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-08-02 | GSE182467 | GEO
Project description:Colorectal cancer is one of the most common cancers worldwide with increasing incidence, the presence of metastasis is one of the major causes for poor outcome. BEX2 has been reported to be involved in tumor development in several types of cancer, but is poorly understood in metastatic colorectal cancer. Here we demonstrated that knockout of BEX2 resulted in the enhancement of the migratory and metastatic potential of colorectal cancer cells in vivo and in vitro, re-expression of BEX2 in knockout cells could reverse the migratory enhancement. Expression profile chip indicated that hedgehog signaling pathway was activated after knockout of BEX2, and hedgehog Signaling inhibitor GANT61 and GDC-0449 could somehow reverse the migratory enhancement of BEX2-/- colorectal cancer cells. We also demonstrated that it is the nucleus translocation of Zic2 after BEX2 silenced, that activated hedgehog signaling pathway, while knockdown Zic2 could also abrogated migratory enhancement of BEX2-/- cells. In summary, our findings suggest that BEX2 is a negative modulator of hedgehog signaling pathway by retaining Zic2 in the cytoplasm of colorectal cancer cells, thus to inhibit colorectal cancer cell migration and metastasis.
2019-12-19 | GSE112590 | GEO
Project description:Transcriptional regulation is critically involved in colorectal cancer (CRC) pathogenesis, the mechanism of which remains incompletely understood. Here, we report that core-binding factor β (CBFβ) is commonly upregulated in human colorectal cancer and is associated with the survival rate of CRC patients. Immunohistochemistry (IHC) analysis of RUNX1-3 expression in CRC patients and other in vitro data revealed that CBFβ promotes cell proliferation and liver metastasis in a RUNX2-dependent way. Transcriptome sequencing, ChIP-seq and promoter-binding experiments demonstrated that the CBFβ/RUNX2 complex could activate the transcription of OPN, FAM129A and UPP1. Furthermore, CBFβ significantly promoted tumor growth and lung metastasis in a mouse xenograft model and an orthotopic liver metastasis model of CRC. Additionally, we identified that tumor-suppressive miR-143/145 could synergistically target CBFβ by specifically binding to its 3’-UTR region. An inverse correlation between miR-143/145 and CBFβ was verified in CRC patients. Our results represent the first report describing a mechanistic role for CBFβ-RUNX2 in the transcriptional activation of OPN, FAM129A and UPP1 in controlling colorectal cancer development, which may offer prognostic and therapeutic opportunities.
2021-11-10 | GSE153682 | GEO