Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA236383 | ENA |
REPOSITORIES: ENA
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Project description:Oct4, a key transcription factor for maintaining the pluripotency and self-renewal of stem cells has been reported previously. It also plays an important role in tumor proliferation and apoptosis, but the role of Oct4 been in tumor metastasis is still not very clear. Here, we found that ectopic expression of Oct4 in breast cancer cells can inhibit their migration and invasion. Detailed examinations revealed that Oct4 up-regulates expression of E-cadherin, indicative of its inhibitory role in epithelial-mesenchymal transition (EMT). RNA-sequence assay showed that Oct4 down-regulates expression of Rnd1. As an atypical Rho protein, Rnd1 can affect cytoskeleton rearrangement and regulate cadherin-based cell-cell adhesion by antagonizing the typical Rho protein, RhoA. Ectopic expression of Rnd1 in MDA-MB-231 cells changes cell morphology which influences cell adhesion and increases migration. It is reported that EMT is accompanied by cytoskeleton remodeling, we hypothesized that Rnd1 may play a role in regulating EMT. Over-expression of Rnd1 can partly rescue the inhibitory effects induced by Oct4, not only migration and invasion, but also in E-cadherin level and cellular morphology. Furthermore, silencing of Rnd1 can up-regulate the expression of E-cadherin in MDA-MB-231 cells. These results present evidence that ectopic expression of Oct4 increases E-cadherin and inhibits metastasis, effects which may be related to Rnd1 associated cell-cell adhesion in breast cancer cells. Examination of mRNA profiles in MDA-MB-231 cells with OCT4 overexpressing
2014-01-25 | E-GEOD-54392 | biostudies-arrayexpress
Project description:Oct4, a key transcription factor for maintaining the pluripotency and self-renewal of stem cells has been reported previously. It also plays an important role in tumor proliferation and apoptosis, but the role of Oct4 been in tumor metastasis is still not very clear. Here, we found that ectopic expression of Oct4 in breast cancer cells can inhibit their migration and invasion. Detailed examinations revealed that Oct4 up-regulates expression of E-cadherin, indicative of its inhibitory role in epithelial-mesenchymal transition (EMT). RNA-sequence assay showed that Oct4 down-regulates expression of Rnd1. As an atypical Rho protein, Rnd1 can affect cytoskeleton rearrangement and regulate cadherin-based cell-cell adhesion by antagonizing the typical Rho protein, RhoA. Ectopic expression of Rnd1 in MDA-MB-231 cells changes cell morphology which influences cell adhesion and increases migration. It is reported that EMT is accompanied by cytoskeleton remodeling, we hypothesized that Rnd1 may play a role in regulating EMT. Over-expression of Rnd1 can partly rescue the inhibitory effects induced by Oct4, not only migration and invasion, but also in E-cadherin level and cellular morphology. Furthermore, silencing of Rnd1 can up-regulate the expression of E-cadherin in MDA-MB-231 cells. These results present evidence that ectopic expression of Oct4 increases E-cadherin and inhibits metastasis, effects which may be related to Rnd1 associated cell-cell adhesion in breast cancer cells.
2014-01-25 | GSE54392 | GEO
Project description:We identified the Rho family GTPase Rnd1 as a candidate breast tumor suppressor by using bioinformatics analysis in conjunction with iRNA silencing. Upon silencing of Rnd1, normal mammary epithelial cells underwent a complete EMT but eventually became senescent, suggesting that they had experienced an oncogenic insult. Expression of c-Myc rescued the Rnd1-depleted cells from senescence by suppressing p27Kip and it enabled their neoplastic conversion. The resulting cells were able to grow in soft agar and to form invasive, multi-acinar structures in 3D Matrigel. Silencing of Rnd1 promoted disruption of epithelial adhesion and polarity in xenograft models. In contrast, expression of Rnd1 inhibited tumor development. Mechanistic studies revealed that Rnd1 suppresses Ras signaling and prevents the EMT by activating the Ras-GAP domain of Plexin B1. Finally, analysis of clinical samples and cancer cell lines provided evidence that gene deletion, epigenetic silencing, and missense mutations contribute to inactivate RND1 in a subset of human breast cancers. These results indicate that Rnd1 promotes epithelial adhesion and polarity and suppresses oncogenesis by restraining unscheduled activation of Ras. genomic DNA from 96 breast cancer tissues and 8 normal mammary tissues were extracted and subjected to SOLID deep sequencing for exons of the RND1 gene to identify tumor-associated mutations with the amino acid exchanges There were two separate SOLID runs (0136 and 0270), on the same 96 tumors. The pools are indicated by "A1", "A2", "B1", etc.
2014-01-01 | E-GEOD-43828 | biostudies-arrayexpress
Project description:We identified the Rho family GTPase Rnd1 as a candidate breast tumor suppressor by using bioinformatics analysis in conjunction with iRNA silencing. Upon silencing of Rnd1, normal mammary epithelial cells underwent a complete EMT but eventually became senescent, suggesting that they had experienced an oncogenic insult. Expression of c-Myc rescued the Rnd1-depleted cells from senescence by suppressing p27Kip and it enabled their neoplastic conversion. The resulting cells were able to grow in soft agar and to form invasive, multi-acinar structures in 3D Matrigel. Silencing of Rnd1 promoted disruption of epithelial adhesion and polarity in xenograft models. In contrast, expression of Rnd1 inhibited tumor development. Mechanistic studies revealed that Rnd1 suppresses Ras signaling and prevents the EMT by activating the Ras-GAP domain of Plexin B1. Finally, analysis of clinical samples and cancer cell lines provided evidence that gene deletion, epigenetic silencing, and missense mutations contribute to inactivate RND1 in a subset of human breast cancers. These results indicate that Rnd1 promotes epithelial adhesion and polarity and suppresses oncogenesis by restraining unscheduled activation of Ras.
2014-01-01 | GSE43828 | GEO
Project description:Breast cancer metastasis is driven by profound remodeling of the intracellular cytoskeleton enabling efficient cell migration. Anillin is a unique cytoskeletal scaffolding protein that regulates actin filaments, microtubules, septin polymers and Rho GTPases. Anillin is markedly overexpressed in breast cancer and other solid cancer, however its functions in cancer cells remain poorly understood. This study aims at investigating the roles of anillin in regulating breast cancer cell migration, invasion and metastasis. CRISPR/Cas9 technology was used to deplete anillin in highly metastatic MDA-MB-231and BT549 cells and to overexpress it in poorly invasive MCF10AneoT cells. These loss-of-function and gain-of-function studies demonstrated that anillin is necessary and sufficient to accelerate migration, invasion and anchorage-independent growth of breast cancer cells in vitro. Furthermore, loss of anillin markedly attenuated both primary tumor growth and metastasis of breast cancer in vivo. In breast cancer cells, anillin was localized in the nucleus, however anillin knockout affected the cytoplasmic/cortical events such as the organization of actin cytoskeleton and cell-matrix adhesions. This was accompanied by a global transcriptional reprogramming of anillin-depleted breast cancer cells that resulted in suppression of their stemness and induction of the mesenchymal to epithelial trans-differentiation. Such trans-differentiation was manifested by upregulation of basal keratins along with increased expression of E-cadherin and P-cadherin. Knockdown of E-cadherin reversed attenuated migration and invasion of anillin-deficient cells. Our study provides the first evidence that anillin plays causal roles in breast cancer development and metastasis in vitro and in vivo and unravels novel functions of anillin in regulating breast cancer stemness and differentiation.
2020-01-01 | GSE131120 | GEO
Project description:Investigation of breast cancer-associated mutations in RND1 gene
| PRJNA188274 | ENA
Project description:The ATP binding cassette (ABC) transporter family is widely distributed in vertebrates and is essential for drug resistance, cell signaling and energy homeostasis. There is growing evidence that various ABC transporters contribute to the growth and development of tumors but relatively little is known about how the ABC transporter family behaves in hepatocellular carcinoma (HCC). ABCC6 transporter was downregulated in HCC tissues and that it was associated with successful treatment for HCC patients. Cellular model studies have shown that ABCC6 plays a role in the migration and cytoskeleton rearrangement of HepG2 hepatocarcinoma cells, highlighting its role in cancer biology. Abcc6-silenced HepG2 cells are used as cell model to obtain more deep information about the molecular mechanisms underlying the observed results. MTT and colony formation assays, showed the effects of Abcc6 on HepG2 cell proliferation. Western blotting analysis, real-time PCR, and immunofluorescence were used to find the E-cadherin, Vimentin, and N-cadherin markers associated with the epithelial-to-mesenchymal transition (EMT). Colony formation experiments in the current study showed that Abcc6 decreased HepG2 cell viability. The migratory and invasion activities were dramatically slowed down by Abcc6 silencing, according to the Transwell and wound-healing assays. In tumor cells, EMT has been shown to be crucial for enhancing migration and invasion and is frequently characterized by a loss of epithelial markers (E-cadherin) and an increase in mesenchymal markers (Vimentin and N-cadherin). In the western blotting examination, E-cadherin expression was considerably elevated compared to the control group, while N-cadherin and Vimentin expression were downregulated. This led to the hypothesis that the underlying mechanism of Abcc6 knockdown prevents migration and invasion in HepG2 cells and is linked to the suppression of EMT. In conclusion all evidence suggested that ABC transporters play a more active role in cancer biology.
2024-01-02 | E-MTAB-13154 | biostudies-arrayexpress
Project description:Intracellular and cell surface molecules are an essential part of the innate immune system. We describe a novel cellular defense mechanism based upon a membrane-associated protein RND1. RND1 belongs to the Rho GTPase family, but unlike other members, it is constitutively active. We show that RND1 is induced by pro-inflammatory cytokines during viral and bacterial infections and provides protection against these pathogens through two distinct mechanisms.
2022-06-21 | GSE185216 | GEO
Project description:Background: E-cadherin is an adherens junction protein that forms homophilic intercellular contacts in epithelial cells while also interacting with the intracellular cytoskeletal networks. It has roles including establishment and maintenance of cell polarity, differentiation, migration and signalling in cell proliferation pathways. Its downregulation is commonly observed in epithelial tumours and is a hallmark of the epithelial to mesenchymal transition (EMT). Methods: To improve our understanding of how E-cadherin loss contributes to tumorigenicity, we investigated the impact of its elimination from the non-tumorigenic breast cell line MCF10A. We performed cell-based assays and whole genome RNAseq to characterize an isogenic MCF10A cell line that is devoid of CDH1 expression due to an engineered homozygous 4bp deletion in CDH1 exon 11. Results: The E-cadherin-deficient line, MCF10A CDH1-/- showed subtle morphological changes, weaker cell-substrate adhesion, delayed migration, but retained cell-cell contact, contact growth inhibition and anchorage-dependent growth. Within the cytoskeleton, the apical microtubule network in the CDH1-deficient cells lacked the radial pattern of organization present in the MCF10A cells and F-actin formed thicker, more numerous stress fibres in the basal part of the cell. Whole genome RNAseq identified compensatory changes in the genes involved in cell-cell adhesion while genes involved in cell-substrate adhesion, notably ITGA1, COL8A1, COL4A2 and COL12A1, were significantly downregulated. Key EMT markers including CDH2, FN1, VIM and VTN were not upregulated although increased expression of proteolytic matrix metalloprotease and kallikrein genes was observed. Conclusions: Overall, our results demonstrated that E-cadherin loss alone was insufficient to induce an EMT or enhance transforming potential in the non-tumorigenic MCF10A cells but was associated with broad transcriptional changes associated with tissue remodelling. Examination of the impact of E-cadherin (CDH1) loss in an isogenic pair of breast cell lines.
2014-08-01 | E-GEOD-59317 | biostudies-arrayexpress
Project description:Rho-GTPases are small GTP-binding proteins that contribute to the epithelial-to-mesenchymal transition by regulating several cellular processes including organization of the actin cytoskeleton, cell motility, transcription, and cell proliferation. Overexpression of RhoC-GTPases (RhoC) in breast cancer has been implicated in poor disease prognosis due to increased cancer cells invasion, migration, and motility, which warranted its consideration as a therapeutic target for inhibiting breast cancer metastasis. Using silencing RNA (siRNA) molecules to knockdown RhoC expression is a promising approach to inhibit breast cancer metastases.
2015-02-11 | ST000282 | MetabolomicsWorkbench