Agrin Mediates Angiogenesis in the Tumor Microenvironment

Chakraborty, Sanjoy; Njah, Kizito; Hong, Wanjin

doi:10.1016/j.trecan.2019.12.002

Cited by 35 publications

(29 citation statements)

References 16 publications

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“…ECM stiffness can be sensed by cells through focal adhesions, as cells use integrin to pull integrin ligands in the ECM. In addition to common integrin ligands such as collagens and fibronectin, an ECM proteoglycan, Agrin, also act as an extracellular mediator of matrix mechanotransduction to regulate YAP/TAZ via integrins, its specific membrane receptor LRP4, and the actin cytoskeleton ( Chakraborty et al, 2017 ; Chakraborty et al, 2020 ). Similarly, matricellular protein thrombospondin-1, acts through integrin-1 and the Hippo pathway, but not actin cytoskeleton, to activate YAP/TAZ ( Yamashiro et al, 2020 ).…”

Section: Yap and Taz Are At The Center Stage Of Mechanotransductionmentioning

confidence: 99%

“…It is speculated that YAP/TAZ hyperactivation is required for cancer cells to overdrive the mechanical checkpoints for growth ( Aragona et al, 2013 ). In addition to cancer cells and cancer-associated fibroblasts, ECM stiffening during tumor progression induces vascular cell growth and allows blood vessel infiltration, potentially through the Agrin-YAP-dependent mechanism ( Chakraborty et al, 2020 ). Indeed, it has recently been shown that the increases in tissue rigidity at metastatic sites enhance cancer angiogenesis and elevate their resistance to anti-angiogenesis therapy ( Shen et al, 2020 ).…”

Section: Mechanoregulation Of Yap/taz In Human Diseasesmentioning

confidence: 99%

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Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression

Cai

Wang

Meng

2021

Front. Cell Dev. Biol.

155

118

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Biophysical cues, such as mechanical properties, play a critical role in tissue growth and homeostasis. During organ development and tissue injury repair, compressive and tensional forces generated by cell-extracellular matrix or cell-cell interaction are key factors for cell fate determination. In the vascular system, hemodynamic forces, shear stress, and cyclic stretch modulate vascular cell phenotypes and susceptibility to atherosclerosis. Despite that emerging efforts have been made to investigate how mechanotransduction is involved in tuning cell and tissue functions in various contexts, the regulatory mechanisms remain largely unknown. One of the challenges is to understand the signaling cascades that transmit mechanical cues from the plasma membrane to the cytoplasm and then to the nuclei to generate mechanoresponsive transcriptomes. YAP and its homolog TAZ, the Hippo pathway effectors, have been identified as key mechanotransducers that sense mechanical stimuli and relay the signals to control transcriptional programs for cell proliferation, differentiation, and transformation. However, the upstream mechanosensors for YAP/TAZ signaling and downstream transcriptome responses following YAP/TAZ activation or repression have not been well characterized. Moreover, the mechanoregulation of YAP/TAZ in literature is highly context-dependent. In this review, we summarize the biomechanical cues in the tissue microenvironment and provide an update on the roles of YAP/TAZ in mechanotransduction in various physiological and pathological conditions.

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Section: Yap and Taz Are At The Center Stage Of Mechanotransductionmentioning

confidence: 99%

Section: Mechanoregulation Of Yap/taz In Human Diseasesmentioning

confidence: 99%

Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression

Cai

Wang

Meng

2021

Front. Cell Dev. Biol.

155

118

View full text Add to dashboard Cite

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“…Fibrosis is mediated by activated cancer-associated fibroblasts and is a complex process that involves excessive deposition and reorganization of the extracellular matrix (ECM), leading to epithelial-to-mesenchymal transition (EMT) reprogramming. For example, a remodeled, stiff ECM can support angiogenesis with abnormal vasculature, leading to a corrupt TME which promotes tumor dissemination [74]. In this regard, the function of lysyl oxidase (LOX) family members on a pro-tumoral TME of HCC by remodeling the ECM was recently noted [75].…”

Section: Fibrosismentioning

confidence: 99%

New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics

Yang

Chang

et al. 2021

JPM

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Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.

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“…33,45 In addition, agrin promotes angiogenesis in cancer progression, which may imply that agrin can improve the neural plastic niche and contribute to sypaptogenesis. 46 Physical exercise is an efficient and natural way to enhance neurogenesis and synaptogenesis in both the normal and injured brain. A recent study from the Kai Chen group indicated that chronic treadmill exercise increased dendritic spines, promoted oligodendrogenesis and axonal myelination, and improved motor learning function through activating the mechanistic target of the rapamycin (mTOR) pathway in mouse motor cortex.…”

Section: Discussionmentioning

confidence: 99%

“…33,45 In addition, agrin promotes angiogenesis in cancer progression, which may imply that agrin can improve the neural plastic niche and contribute to sypaptogenesis. 46…”

Section: Discussionmentioning

confidence: 99%

Agrin Involvement in Synaptogenesis Induced by Exercise in a Rat Model of Experimental Stroke

Zhang

Yang

et al. 2020

Neurorehabil Neural Repair

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Background Agrin is a proteoglycan that aggregates nicotinic acetylcholine receptors (AChRs) on neuromuscular junctions and takes part in synaptogenesis in the development of the central nervous system. However, its effects on neural repair and synaptogenesis after stroke are still unclear. Objective This study aimed to investigate the effects of agrin on neural repair and synaptogenesis after stroke and the effects of exercise on this process in vivo and in vitro. Methods Exercise with gradually increased intensity was initiated at 1 day after middle cerebral artery occlusion (MCAO) for a maximum of 14 days. Neurological deficit scores and foot fault tests were used to assess the behavioral recovery. Western blotting, immunofluorescence, and electron microscopic images were used to detect the expression of agrin, synaptogenesis-related proteins, and synaptic density in vivo. In vitro, the ischemic neuron model was established via oxygen-glucose deprivation (OGD). The lentivirus overexpressed agrin and CREB inhibitor were used to investigate the mechanism by which agrin promoted synaptogenesis. Results Exercise promoted behavioral recovery and this beneficial role was linked to the upregulated expression of agrin and increased synaptic density. Overexpressed agrin promoted synaptogenesis in OGD neuron, CREB inhibitor downregulated the expression of agrin and hampered synaptogenesis in cultured neurons. Conclusions These results indicated that exercise poststroke improved the recovery of behavioral function after stroke. Synaptogenesis was an important and beneficial factor, and agrin played a critical role in this process and could be a potential therapeutic target for the treatment of stroke and other nervous system diseases.

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Agrin Mediates Angiogenesis in the Tumor Microenvironment

Cited by 35 publications

References 16 publications

Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression

Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression

New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics

Agrin Involvement in Synaptogenesis Induced by Exercise in a Rat Model of Experimental Stroke

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