Cancer-associated fibroblast (CAF)-derived IL32 promotes breast cancer cell invasion and metastasis via integrin β3–p38 MAPK signalling

Wen, Siyang; Hou, Yixuan; Fu, Lianshe; Xi, Lei; Yang, Dan; Zhao, Mingqiu; Qin, Yilu; Sun, Kai; Teng, Yong; Liu, Manran

doi:10.1016/j.canlet.2018.10.015

Cited by 243 publications

(165 citation statements)

References 50 publications

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“…Integrin β3, a well-known member of the integrin family, has been studied extensively in cell proliferation and metastasis in various cancers [15,16]. Recent studies have shown that integrin β3 plays an important role in cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia-induced apoptosis via regulating the PTEN/Akt/mTOR and ERK1/2 pathways

et al. 2020

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Objective: Integrin β3 is one of the main integrin heterodimer receptors on the surface of cardiac myocytes. Our previous studies showed that hypoxia induces apoptosis and increases integrin β3 expression in cardiomyocytes. However, the exact mechanism by which integrin β3 protects against apoptosis remains unclear. Hence, the present investigation aimed to explore the mechanism of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis.Methods: Stable cells and in vivo acute and chronic heart failure rat models were generated to reveal the essential role of integrin β3 in cardiomyocyte proliferation and apoptosis. Western blotting and immunohistochemistry were employed to detect the expression of integrin β3 in the stable cells and rat cardiac tissue. Flow cytometer was used to investigate the role of integrin β3 in hypoxia-induced cardiomyocyte apoptosis. Confocal microscopy was used to detect the localization of integrin β3 and integrin αv in cardiomyocytes. Results: A cobaltous chloride-induced hypoxic microenvironment stimulated cardiomyocyte apoptosis and increased integrin β3 expression in H9C2 cells, AC16 cells, and cardiac tissue from acute and chronic heart failure rats. The overexpression of integrin β3 promoted cardiomyocyte proliferation, whereas silencing integrin β3 expression resulted in decreased cell proliferation in vitro. Furthermore, knocking down integrin β3 expression using shRNA or the integrin β3 inhibitor cilengitide exacerbated cobaltous chloride-induced cardiomyocyte apoptosis, whereas overexpression of integrin β3 weakened cobaltous chloride-induced cardiomyocytes apoptosis. We found that integrin β3 promoted cardiomyocytes proliferation through the regulation of the PTEN/Akt/mTOR and ERK1/2 signaling pathways. In addition, we found that knockdown of integrin αv or integrin β1 weakened the effect of integrin β3 in cardiomyocyte proliferation. Conclusion: Our findings revealed the molecular mechanism of the role of integrin β3 in cardiomyocyte proliferation and hypoxia-induced cardiomyocyte apoptosis, providing new insights into the mechanisms underlying myocardial protection.

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Section: Discussionmentioning

confidence: 99%

Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia-induced apoptosis via regulating the PTEN/Akt/mTOR and ERK1/2 pathways

et al. 2020

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“…Deregulated ERK signaling pathway leads to uncontrolled cell proliferation and a reduction in apoptosis (89). in MM-231 Bc cells, upregulated p38 pathway is linked to the increased proliferation and migration (71) and contribute to cancer cell invasion (90). Therefore, highlighting GoSS effects on MAPKs implies its particularity for TnBc.…”

Section: + Goss -----------------------------------------------------mentioning

confidence: 99%

Molecular mechanism of gossypol mediating CCL2 and IL‑8 attenuation in triple‑negative breast cancer cells

et al. 2020

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chronic inflammation associated with cancer is characterized by the production of different types of chemokines and cytokines. in cancer, numerous signaling pathways upregulate the expression levels of several cytokines and evolve cells to the neoplastic state. Therefore, targeting these signaling pathways through the inhibition of distinctive gene expression is a primary target for cancer therapy. The present study investigated the anticancer effects of the natural polyphenol gossypol (GoSS) in triple-negative breast cancer (TnBc) cells, the most aggressive breast cancer type with poor prognosis. GoSS effects were examined in two TnBc cell lines: Mda-MB-231 (MM-231) and Mda-MB-468 (MM-468), representing caucasian americans (ca) and african americans (aa), respectively. The obtained ic 50 s revealed no significant difference between the two cell lines' response to the compound. However, the use of microarray assays for cytokine determination indicated the ability of GoSS to attenuate the expression levels of cancer-related cytokines in the two cell lines. although GoSS did not alter ccl2 expression in MM-468 cells, it was able to cause 30% inhibition in TnF-α-stimulated MM-231 cells. additionally, il-8 was not altered by GoSS treatment in MM-231 cells, while its expression was inhibited by 60% in TnF-α-activated MM-468 cells. eliSa assays supported the microarray data and indicated that ccl2 expression was inhibited by 40% in MM-231 cells, and il-8 expression was inhibited by 50% in MM-468 cells. Furthermore, in MM-231 cells, GoSS inhibited ccl2 release via the repression of iKBKe, CCL2 and MAPK1 gene expression. additionally, in MM-468 cells, the compound downregulated the release of il-8 through repressing IL-8, MAPK1, MAPK3, CCDC88A, STAT3 and PIK3CD gene expression. in conclusion, the data obtained in the present study indicate that the polyphenol compound GoSS may provide a valuable tool in TnBc therapy.

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“…16 It was reported to promote breast cancer cell invasion and metastasis via integrin β3/p38 mitogen-activated protein kinase (MAPK) signalling. 17 We therefore investigated the role of IL32 in OSCC migration and invasion and found that overexpression of IL32 in UM-SCC6 cells stimulated both of these behaviours ( Figure 5A,B and S6A). On the contrary, migration and invasion of UM-SCC6-M cells were suppressed by IL32 knockdown (Figure S6A-C).…”

Section: Il32 Promoted Oscc Cell Migration and Invasion By Activatimentioning

confidence: 99%

MicroRNA‐29b‐3p suppresses oral squamous cell carcinoma cell migration and invasion via IL32/AKT signalling pathway

Wen

Kou

et al. 2019

J Cellular Molecular Medi

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Oral squamous cell carcinoma (OSCC) is aggressive accompanied with poor prognosis. We previously isolated the most invasive cells resembling the invasive tumour front by microfluidic technology and explored their differentially expressed microRNAs (miRNAs) in our previous work. Here, we verified the miR‐29b‐3p as a guarder that suppressed migration and invasion of OSCC cells and was down‐regulated in the most invasive cells. Besides that, the invasion suppression role of miR‐29b‐3p was achieved through the IL32/AKT pathway. Thus, miR‐29b‐3p and IL32 might serve as therapeutic targets for blocking the progression and improving the outcome of OSCC.

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Cancer-associated fibroblast (CAF)-derived IL32 promotes breast cancer cell invasion and metastasis via integrin β3–p38 MAPK signalling

Cited by 243 publications

References 50 publications

Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia-induced apoptosis via regulating the PTEN/Akt/mTOR and ERK1/2 pathways

Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia-induced apoptosis via regulating the PTEN/Akt/mTOR and ERK1/2 pathways

Molecular mechanism of gossypol mediating CCL2 and IL‑8 attenuation in triple‑negative breast cancer cells

MicroRNA‐29b‐3p suppresses oral squamous cell carcinoma cell migration and invasion via IL32/AKT signalling pathway

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