ANKRD1 promotes breast cancer metastasis by activating NF-κB-MAGE-A6 pathway
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PROVIDER: PRJNA1140104 | ENA |
REPOSITORIES: ENA
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Project description:Early detection and surgical excision of tumors have helped improve the survival rate of 24 patients with breast cancer. However, patients with metastatic cancer have a poor prognosis. In 25 this study, we propose that ANKRD1 promotes metastasis of breast cancer. ANKRD1 was found 26 to be highly expressed in the MDA-MB-231 and MDA-LM-2 malignant metastatic breast cancer 27 cell lines compared to the non-metastatic breast cancer cells (MCF-7, ZR-75-30, T47D) and normal 28 breast cancer cells (MCF-10A). Furthermore, high-grade tumors showed increased levels of 29 ANKRD1 compared to low-grade tumors. Both in vitro and in vivo functional studies demon- 30 strated the essential role of ANKRD1 in cancer cell migration and invasion. The previous studies 31 have suggested an important role of NF-κB and MAGE-A6 in breast cancer metastasis, but the 32 upstream regulators of this axis are not well characterized. Our study suggests that ANKRD1 33 promotes metastasis of breast cancer by activating NF-κB as well as MAGE-A6 signaling. Our 34 findings show that ANKRD1 is a potential therapeutic target and a diagnostic marker for breast 35 cancer metastasis.
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Project description:Stromal cell senescence plays a crucial role in activating cancer-associated fibroblasts (CAFs). The Androgen receptor (AR) function oversees cellular senescence and CAF activation. Here, we identify the mesenchymal-specific transcriptional coregulator ANKRD1 as a key driver of CAF conversion. ANKRD1 is strongly upregulated in CAFs and under direct negative control of AR, and its loss impairs the pro-tumorigenic potential of CAFs. ANKRD1 controls a CAF-specific gene expression program and is associated with poorer survival of HNSCC, lung, and cervical SCC patients. Mechanistically, ANKRD1 binds to the chromatin on CAF gene regulatory regions in a complex with the AP1 transcription factor family. We show that ANKRD1 enhances the AP1 DNA binding activity to CAF gene promoters. Targeting ANKRD1 with the FANA antisense oligonucleotides reverts CAFs into a normal fibroblast, disrupts AP1 complex formation, and blocks CAF’s pro-tumorigenic potential in an orthotopic model of SCC, thus representing an exciting target for stroma-oriented cancer therapy.
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Project description:Stromal cell senescence plays a crucial role in activating cancer-associated fibroblasts (CAFs). The Androgen receptor (AR) function oversees cellular senescence and CAF activation. Here, we identify the mesenchymal-specific transcriptional coregulator ANKRD1 as a key driver of CAF conversion. ANKRD1 is strongly upregulated in CAFs and under direct negative control of AR, and its loss impairs the pro-tumorigenic potential of CAFs. ANKRD1 controls a CAF-specific gene expression program and is associated with poorer survival of HNSCC, lung, and cervical SCC patients. Mechanistically, ANKRD1 binds to the chromatin on CAF gene regulatory regions in a complex with the AP1 transcription factor family. We show that ANKRD1 enhances the AP1 DNA binding activity to CAF gene promoters. Targeting ANKRD1 with the FANA antisense oligonucleotides reverts CAFs into a normal fibroblast, disrupts AP1 complex formation, and blocks CAF’s pro-tumorigenic potential in an orthotopic model of SCC, thus representing an exciting target for stroma-oriented cancer therapy.
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Project description:To define the role of MAGE-A1 in melanoma growth and metastasis, we performed RNA-seq analysis on MAGE-A1 overexpression (OE) and knockdown (KD) models in A375 human melanoma cell line. Our results revealed that overexpression of MAGE-A1 dramatically promoted proliferation, migration, and invasion of human melanoma cells in vitro and down-regulated of MAGE-A1 inhibited tumor cell proliferation and invasion. Furthermore, MAGE-A1 exerts its tumor promoting activity via activating including ERK-MAPK signaling pathway by RNA-seq analysis.
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Project description:To define the role of MAGE-A1 in melanoma growth and metastasis, we performed RNA-seq analysis on MAGE-A1 overexpression (OE) and knockdown (KD) models in A375 human melanoma cell line. Our results revealed that overexpression of MAGE-A1 dramatically promoted proliferation, migration, and invasion of human melanoma cells in vitro and down-regulated of MAGE-A1 inhibited tumor cell proliferation and invasion. Furthermore, MAGE-A1 exerts its tumor promoting activity via activating including ERK-MAPK signaling pathway by RNA-seq analysis. mRNA profiles of MAGE-A1 over expression (OE), knockdown (KD), pcDNA-vector control, and pRNAT-scramble control in A375 cell line were generated using Ion torrent
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Project description:Stromal cell senescence plays a crucial role in activating cancer-associated fibroblasts (CAFs). The Androgen receptor (AR) function oversees cellular senescence and CAF activation. Here, we identify the mesenchymal-specific transcriptional coregulator ANKRD1 as a key driver of CAF conversion. ANKRD1 is strongly upregulated in CAFs and under direct negative control of AR, and its loss impairs the pro-tumorigenic potential of CAFs. ANKRD1 controls a CAF-specific gene expression program and is associated with poorer survival of HNSCC, lung, and cervical SCC patients. Mechanistically, ANKRD1 binds to the chromatin on CAF gene regulatory regions in a complex with the AP1 transcription factor family. We show that ANKRD1 enhances the AP1 DNA binding activity to CAF gene promoters. Targeting ANKRD1 with the FANA antisense oligonucleotides reverts CAFs into a normal fibroblast, disrupts AP1 complex formation, and blocks CAF’s pro-tumorigenic potential in an orthotopic model of SCC, thus representing an exciting target for stroma-oriented cancer therapy.
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