Conditional knockdown of integrin beta-3 reveals its involvement in osteolytic and soft tissue lesions of breast cancer skeletal metastasis

Kovacheva, Marineta; Zepp, Michael; Berger, Stefan; Berger, Martin R.

doi:10.1007/s00432-020-03428-y

Cited by 24 publications

(22 citation statements)

References 29 publications

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“…Integrin α5β1 and αvβ3 can bind with fibronectin [ 65 ] and play crucial roles in wound healing [ 66 , 67 , 68 ], while cell adhesion to collagen is mediated by integrin α1β1 [ 69 ]. The β subunits form heterodimers with α integrins that can promote cell migration, which has been reported to participate in the development of cancer [ 70 , 71 ], the immune system [ 72 ], and in tissue repair [ 73 , 74 ]. β1 knockout in fibroblasts reduced cell functions such as cell adhesion, spread, differentiation, expression of collagen and connective tissue growth factor, cutaneous wound closure, and ECM deposition [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Cutaneous Regeneration Mechanism of β-Sheet Silk Fibroin in a Rat Burn Wound Healing Model

et al. 2021

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Therapeutic dressings to enhance burn wound repair and regeneration are required. Silk fibroin (SF), a natural protein, induces cell migration and serves as a biomaterial in various dressings. SF dressings usually contain α-helices and β-sheets. The former has been confirmed to improve cell proliferation and migration, but the wound healing effect and related mechanisms of β-sheet SF remain unclear. We investigated the effects of β-sheet SF in vivo and in vitro. Alcohol-treated α-helix SF transformed into the β-sheet form, which promoted granulation formation and re-epithelialization when applied as lyophilized SF dressing (LSFD) in a rat burn model. Our in vitro results showed that β-sheet SF increased human dermal fibroblast (HDF) migration and promoted the expression of extracellular matrix (ECM) proteins (fibronectin and type III collagen), matrix metalloproteinase-12, and the cell adhesion molecule, integrin β1, in rat granulation tissue and HDFs. This confirms the role of crosstalk between integrin β1 and ECM proteins in cell migration. In summary, we demonstrated that β-sheet SF facilitates tissue regeneration by modulating cell adhesion molecules in dermal fibroblasts. LSFD could find clinical application for burn wound regeneration. Moreover, β-sheet SF could be combined with anti-inflammatory materials, growth factors, or antibiotics to develop novel dressings.

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Section: Discussionmentioning

confidence: 99%

Cutaneous Regeneration Mechanism of β-Sheet Silk Fibroin in a Rat Burn Wound Healing Model

et al. 2021

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“…Additionally, the heterodimer αvβ3 in tumor cells is responsible for invasion of the bone and the recruitment of osteoclasts [62]. In a study evaluating the integrin β3 inhibition, anti-proliferative and anti-migratory effects were observed in MDA-MB-231 cells, as well as complete remission of osteolytic lesions in a nude rat model of bone metastasis [63]. There are few studies involving integrin α11 and bone tissue [64].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Response to Acidosis Reveals Its Contribution to Bone Metastasis in Breast Cancer Cells

Yamagata

Freire

Villarinho

et al. 2022

Cells

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Bone is the most common site of metastasis in breast cancer. Metastasis is promoted by acidosis, which is associated with osteoporosis. To investigate how acidosis could promote bone metastasis, we compared differentially expressed genes (DEGs) in MDA-MB-231 cancer cells in acidosis, bone metastasis, and bone metastatic tumors. The DEGs were identified using Biojupies and GEO2R. The expression profiles were assessed with Morpheus. The overlapping DEGs between acidosis and bone metastasis were compared to the bulk of the DEGs in terms of the most important genes and enriched terms using CytoHubba and STRING. The expression of the genes in this overlap filtered by secreted proteins was assessed in the osteoporosis secretome. The analysis revealed that acidosis-associated transcriptomic changes were more similar to bone metastasis than bone metastatic tumors. Extracellular matrix (ECM) organization would be the main biological process shared between acidosis and bone metastasis. The secretome genes upregulated in acidosis, bone metastasis, and osteoporosis-associated mesenchymal stem cells are enriched for ECM organization and angiogenesis. Therefore, acidosis may be more important in the metastatic niche than in the primary tumor. Acidosis may contribute to bone metastasis by promoting ECM organization. Untreated osteoporosis could favor bone metastasis through the increased secretion of ECM organization proteins.

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“…In our study, several independent approaches were adopted to identify novel miR-30a target genes including taking intersection of five prediction databases and GO analysis of candidate genes. Among all the predicted genes in Figure 2A, SOCS1 [43], MYBL2 [44], ITGB3 [45], FOXD1 [46] have been reported to be involved in the progression, metastasis or drug resistance in breast cancer. Especially, Snail has been reported to repress the transcription of E-cadherin and SOX4 could regulate EMT with the same mechanism of Snail [47], they might have interaction through the process of EMT in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

miR-30a/SOX4 Double Negative Feedback Loop is modulated by Disulfiram and regulates EMT and Stem Cell-like properties in Breast Cancer

Liu

Zheng

et al. 2021

J. Cancer

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Background: Both epithelial-to-mesenchymal transition (EMT) and cancer stem cells play important roles in development and progression of breast cancer. MicroRNA (miR)-30 family members have been reported to be associated with the regulation of EMT and stem cell phenotypes, however, the underlying molecular mechanisms are not well understood. Methods: miR-30a stable transfectants of breast cancer cell lines were created using a lentiviral system. Bioinformatics analysis was performed to explore miR-30a target genes and SOX4 was selected and identified by dual luciferase reporter assay. The effects of miR-30a and target gene SOX4 on EMT and CSC phenotypes in breast cancer were explored in vitro and in vivo. Results: Overexpression of miR-30a in breast cancer cells inhibited EMT and CSC phenotypes by targeting SOX4. Luciferase reporter assay confirmed that miR-30a directly targeted 3'UTR of SOX4, and formed a double-negative feedback loop with SOX4. Functional experiments demonstrated that knockdown of SOX4 suppressed EMT and CSC phenotypes of breast cancer cells through TGF-β/SMAD pathway, which was consistent with the inhibitory effects by overexpression of miR-30a. Additionally, we found disulfiram can upregulate miR-30a expression, and high miR-30a expression was associated with a good prognosis in breast cancer patients through TCGA database. Conclusion:Our findings suggest a novel double-negative loop between miR-30a and SOX4 mediated regulation of EMT and CSC features in breast cancer through TGF-β/SMAD pathway, highlighting a novel therapeutic target for breast cancer.

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Conditional knockdown of integrin beta-3 reveals its involvement in osteolytic and soft tissue lesions of breast cancer skeletal metastasis

Cited by 24 publications

References 29 publications

Cutaneous Regeneration Mechanism of β-Sheet Silk Fibroin in a Rat Burn Wound Healing Model

Cutaneous Regeneration Mechanism of β-Sheet Silk Fibroin in a Rat Burn Wound Healing Model

Transcriptomic Response to Acidosis Reveals Its Contribution to Bone Metastasis in Breast Cancer Cells

miR-30a/SOX4 Double Negative Feedback Loop is modulated by Disulfiram and regulates EMT and Stem Cell-like properties in Breast Cancer

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