Transforming Growth Factor-β Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells

Koudelková, Petra; Costina, Victor; Weber, Gerhard; Dooley, Steven; Findeisen, Peter; Winter, Peter; Agarwal, Rahul; Schlangen, Karin; Mikulits, Wolfgang

doi:10.3390/ijms18102119

Cited by 16 publications

(12 citation statements)

References 46 publications

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“…Although T-1 is downstream of TGF-β, the effects of a TGF-β inhibitor on actin cytoskeleton changes were the same as those of T-1 depletion, and both approaches reduced CRC migration (Elsafadi et al, 2020), suggesting that T-1 is a novel target in CRC metastasis. Additionally, T-2 expression was induced with TGF-β stimulation in a Smad4-dependent manner, which explained its role in CRC progression (Ali et al, 2010;Koudelkova et al, 2017).…”

Section: Tgf-β/smad Signaling Pathwaymentioning

confidence: 98%

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

Zhang

et al. 2020

Front. Cell Dev. Biol.

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Transgelins, including transgelin-1 (T-1), transgelin-2 (T-2), and transgelin-3 (T-3), are a family of actin-binding proteins (ABPs) that can alter the structure and morphology of the cytoskeleton. These proteins function by regulating migration, proliferation and apoptosis in many different cancers. Several studies have shown that in various types of tumor cells, including colorectal cancer (CRC) cells, and in the tumor microenvironment, the expression and biological effects of transgelins are diverse and may transform during tumor progression. Previous researches have demonstrated that transgelin levels are positively correlated with metastasis in CRC, and down-regulating their expression can inhibit this process. In advanced disease, T-1 is a tumor activator with increasing expression, and T-2 expression increases with the progression of CRC. Finally, T-3 is only expressed in neurons and is not associated with CRC. This evidence suggests that T-1 and T-2 are potential biomarkers and therapeutic targets for CRC metastasis.

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Section: Tgf-β/smad Signaling Pathwaymentioning

confidence: 98%

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

Zhang

et al. 2020

Front. Cell Dev. Biol.

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“…Similar positive effects on transendothelial migration by TGF-β have been observed in hepatocellular carcinoma (HCC). 94 TGFβ can thus promote migration towards the liver by promoting interactions with CAFs and endothelial cells.…”

Section: Tgf-β Induced Migration Of Tumor Cells Toward the Livermentioning

confidence: 99%

TGF‐β signaling in liver metastasis

Marvin

Heijboer

Dijke

et al. 2020

Clinical & Translational Med

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The presence of liver metastases drastically worsens the prognosis of cancer patients. The liver is the second most prevalent metastatic site in cancer patients, but systemic therapeutic opportunities that target liver metastases are still limited. To aid the discovery of novel treatment options for metastatic liver disease, we provide insight into the cellular and molecular steps required for liver colonization. For successful colonization in the liver, adaptation of tumor cells and surrounding stroma is essential. This includes the formation of a pre-metastatic niche, the creation of a fibrotic and immune suppressive environment, angiogenesis, and adaptation of tumor cells. We illustrate that transforming growth factor β (TGF-β) is a central cytokine in all these processes. At last, we devise that future research should focus on TGF-β inhibitory strategies, especially in combination with immunotherapy. This promising systemic treatment strategy has potential to eliminate distant metastases as the efficacy of immunotherapy will be enhanced.

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“…These results indicate that significant changes during active transmigration are involved in blood vessel invasion of HCC cells. 99 Intriguingly, TGF-β signaling also induces a high expression of the receptor tyrosine kinase Axl in EMT-transformed hepatoma cells. The overexpression of Axl by its ligand Gas6 induces, through the interaction of 14-3-3 ζ, metastatic colonization of epithelial hepatoma cells in vivo.…”

Section: Inducer Of Cancer-stromal Cells Interactionmentioning

confidence: 99%

TGF-β as Multifaceted Orchestrator in HCC Progression: Signaling, EMT, Immune Microenvironment, and Novel Therapeutic Perspectives

et al. 2018

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Therapeutic attempts to treat hepatocellular carcinoma (HCC) frequently result in a poor response or treatment failure. The efficacy of approved drugs and survival expectancies is affected by an ample degree of variability that can be explained at least in part by the enormous between-patient cellular and molecular heterogeneity of this neoplasm. Transforming growth factor-β (TGF-β) is hyperactivated in a large fraction of HCCs, where it influences complex interactive networks covering multiple cell types and a plethora of other local soluble ligands, ultimately establishing several malignancy traits. This cytokine boosts the invasiveness of cancerous epithelial cells through promoting the epithelial-to-mesenchymal transition program, but also skews the phenotype of immune cells toward a tumor-supporting status. Here, we discuss recent strategies pursued to offset TGF-β-dependent processes that promote metastatic progression and immune surveillance escape in solid cancers, including HCC. Moreover, we report findings indicating that TGF-β reduces the expression of the proinflammatory factors CCL4 and interleukin-1β (IL-1β in human ex vivo treated HCC tissues. While this is consistent with the anti-inflammatory properties of TGF-β, whether it is an outright tumor promoter or suppressor is still a matter of some debate. Indeed, IL-1β has also been shown to support angiogenesis and cell invasiveness in some cancers. In addition, we describe an inhibitory effect of TGF-β on the secretion of CCL2 and CXCL1 by HCC-derived fibroblasts, which suggests the existence of an indirect stroma-mediated functional link between TGF-β and downstream immunity.

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Transforming Growth Factor-β Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells

Cited by 16 publications

References 46 publications

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer

TGF‐β signaling in liver metastasis

TGF-β as Multifaceted Orchestrator in HCC Progression: Signaling, EMT, Immune Microenvironment, and Novel Therapeutic Perspectives

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