Targeting TGF-β Signaling in Cancer

Colak, Selçuk; Dijke, Peter ten

doi:10.1016/j.trecan.2016.11.008

Cited by 839 publications

(735 citation statements)

References 110 publications

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“…Other targets include MAPK, TGFβ, and estrogen signaling. These are already used in the treatment of a number of human cancers, including neuronally-derived tumors, and their effectiveness as fibropapillomatosis therapeutics should be further investigated 85–90 . To fully achieve the promise of precision medicine and move toward more targeted treatment, newer generation therapeutics highlighted by our findings, such as vismodegib, should be trialed as anti- fibropapillomatosis treatments.…”

Section: Discussionmentioning

confidence: 99%

Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

et al. 2018

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Wildlife populations are under intense anthropogenic pressures, with the geographic range of many species shrinking, dramatic reductions in population numbers and undisturbed habitats, and biodiversity loss. It is postulated that we are in the midst of a sixth (Anthropocene) mass extinction event, the first to be induced by human activity. Further, threatening vulnerable species is the increased rate of emerging diseases, another consequence of anthropogenic activities. Innovative approaches are required to help maintain healthy populations until the chronic underlying causes of these issues can be addressed. Fibropapillomatosis in sea turtles is one such wildlife disease. Here, we applied precision-medicine-based approaches to profile fibropapillomatosis tumors to better understand their biology, identify novel therapeutics, and gain insights into viral and environmental triggers for fibropapillomatosis. We show that fibropapillomatosis tumors share genetic vulnerabilities with human cancer types, revealing that they are amenable to treatment with human anti-cancer therapeutics.

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Section: Discussionmentioning

confidence: 99%

Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

et al. 2018

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“…Overexpression of several MMPs (MMP-1, MMP-2, and MMP-9) in RCC is associated with tumor stage, histological grade, progression, invasion of microvasculature, and distant metastasis [28]. MMP-9 can degrade collagen and increase the bio-availability of pro-angiogenic factors, such as VEGF and transforming growth factor (TGF)- β [29]. Other studies reported that increased phosphorylation of ERK and enhanced expression of MMP-2 or MMP-9 by treatment with gamma-aminobutyric acid (an inhibitory neurotransmitter) or knockdown of hepatocellular carcinoma-related protein (HCRP) increased the invasive activity of RCC cells [30].…”

Section: Discussionmentioning

confidence: 99%

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity

Chen

Hsieh

Lin

et al. 2017

Cell Physiol Biochem

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Background/Aims: α-mangostin has anti-carcinogenic effects against several cancers. We investigated the molecular mechanism of this compound on the metastasis of human renal carcinoma cells. Methods: Cell viability was measured using the MTT assay, and cell cycle distribution using flow cytometry. A Matrigel-based assay was used to measure in vitro cell migration and invasion. MAPK-related proteins and matrix metalloproteinase (MMP)-9 and MMP-2 expression were measured by western blotting, and MMP2/-9 activities were determined by gelatin zymography. RT-qPCR and a luciferase assay were used to examine the transcriptional activity of MMP-9. Results: α-mangostin inhibited the migration and invasion of RCC cells in a dose-dependent manner, but had no evident cytotoxic effects. Treatment of 786-O cells with α-mangostin inhibited activation of MEK and ERK. Treatment with a specific MEK inhibitor (U0126) enhanced the inhibitory effects of α-mangostin on cell migration and invasion, and the phosphorylation of ERK and MEK. Moreover, α-mangostin inhibited the expression of the MMP-9 mRNA levels as well as the activity of MMP-9 promoter, and these suppressive effects were further enhanced by U0126. Conclusions: Our results suggest that α-mangostin suppresses cell migration and invasion via MEK/ERK/MMP9 pathway, and might be a promising anti-metastatic agent against human renal cell carcinoma.

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“…The dual function of the signalling pathway makes it a challenging target . For an extensive summary of TGF‐β targeting drugs, see the review by Colak et al . Another activated signalling pathway is the PDGFR pathway which can be targeted by the imatinib anticancer drug.…”

Section: The Biological Mechanism Of the Tumour Stroma In Colon Cancermentioning

confidence: 99%

The tumour–stroma ratio in colon cancer: the biological role and its prognostic impact

et al. 2018

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The tumour microenvironment consists of a complex mixture of non-neoplastic cells, including fibroblasts, immune cells and endothelial cells embedded in the proteins of the extracellular matrix. The tumour microenvironment plays an active role in tumour behaviour. By interacting with cancer cells, it influences disease progression and the metastatic capacity of the tumour. Tumours with a high amount of stroma correspond to poor patient prognosis. The tumour-stroma ratio (TSR) is a strong independent prognostic tool in colon cancer and provides additional value to the current clinically used tumour-node-metastasis classification. The TSR is assessed on conventional haematoxylin and eosin-stained paraffin sections at the invasive front of the tumour. Here we review studies demonstrating the prognostic significance of the TSR in solid epithelial tumours with a focus on colon cancer. Moreover, the biological role of the tumour microenvironment during tumour progression and invasion will be discussed, as well as the attempts to target the tumour stroma for therapeutic purposes. We suggest that the TSR can be implemented with little effort and without additional costs in current routine pathology diagnostics owing to its simplicity and reliability.

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Targeting TGF-β Signaling in Cancer

Cited by 839 publications

References 110 publications

Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity

The tumour–stroma ratio in colon cancer: the biological role and its prognostic impact

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