AmotP130 regulates Rho <scp>GTP</scp>ase and decreases breast cancer cell mobility

Chen, Zheling; Jiao, Yang; Shen, Yanwei; Li, Shu‐Ting; Wang, Xin; Lv, Meng; Wang, Bi‐Yuan; Pan, Li; Zhao, Wen; Qiu, Ruiyue; Liu, Yu; Liu, Peijun

doi:10.1111/jcmm.13533

Cited by 7 publications

(5 citation statements)

References 62 publications

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“…Western blotting assay was done as previously described [33]. Following primary antibodies were used: anti-ANG1 (1:1000, Abcam, UK), anti-PDGFB (1:500, Cell Signaling Technology, UK) and anti-β-actin (1:5000, Proteintech, China).…”

Section: Methodsmentioning

confidence: 99%

Tumor vasculature remolding by thalidomide increases delivery and efficacy of cisplatin

Shen

Wang

et al. 2019

J Exp Clin Cancer Res

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Background A promising strategy to overcome the chemoresistance is the tumor blood vessel normalization, which restores the physiological perfusion and oxygenation of tumor vasculature. Thalidomide (Thal) has been shown to increase the anti-tumor effect of chemotherapy agents in solid tumors. However, it is not yet known whether the synergistic effect of Thal combined with other cytotoxic drugs is attributable to tumor vascular normalization. Methods We used two homograft mice models (4 T1 breast tumor model and CT26 colorectal tumor model) to investigate the effect of Thal on tumor growth, microvessel density, vascular physiology, vascular maturity and function, drug delivery and chemosensitivity. Immunofluorescence, immunohistochemistry and scanning electron microscopy were performed to determine the vessel changes. Protein array assay, qPCR and western blotting were used to detect the molecular mechanism by which Thal regulates tumor vascular. Results Here we report that Thal potently suppressed tumor growth, angiogenesis, hypoxia, and vascular permeability in animal models. Thal also induced a regular monolayer of endothelial cells in tumor vessels, inhibiting vascular instability, and normalized tumor vessels by increasing vascular maturity, pericyte coverage and endothelial junctions. The tumor vessel stabilization effect of Thal resulted in a decrease in tumor vessel tortuosity and leakage, and increased vessel thickness and tumor perfusion. Eventually, the delivery of cisplatin was highly enhanced through the normalized tumor vasculature, thus resulting in profound anti-tumor and anti-metastatic effects. Mechanistically, the effects of Thal on tumor vessels were caused in part by its capability to correct the imbalance between pro-angiogenic factors and anti-angiogenic factors. Conclusions Our findings provide direct evidence that Thal remodels the abnormal tumor vessel system into a normalized vasculature. Our results may lay solid foundation for the development of Thal as a novel candidate agent to maximize the therapeutic efficacy of chemotherapeutic drugs for solid tumors.

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Section: Methodsmentioning

confidence: 99%

Tumor vasculature remolding by thalidomide increases delivery and efficacy of cisplatin

Shen

Wang

et al. 2019

J Exp Clin Cancer Res

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“…We hypothesized that Amot-p80 and Amot-p130 have different functions in breast carcinogenesis. In a previous work from our group, we have shown that Amot-p130 decreases the motility of BCa cells 22 . Here, we have investigated the link between the inhibition of metastasis and Amot-p130 in BCa.…”

Section: Introductionmentioning

confidence: 65%

Angiomotin-p130 inhibits β-catenin stability by competing with Axin for binding to tankyrase in breast cancer

et al. 2019

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Growing evidence indicates that Angiomotin (Amot)-p130 and Amot-p80 have different physiological functions. We hypothesized that Amot-p130 is a tumor suppressor gene in breast cancer, in contrast with the canonical oncogenicity of Amot-p80 or total Amot. To clarify the role of Amot-p130 in breast cancer, we performed real-time quantitative PCR, western blotting, flow cytometry, microarray, immunofluorescence, immunoprecipitation, and tumor sphere-formation assays in vitro, as well as tumorigenesis and limited-dilution analysis in vivo. In this study, we showed that Amot-p130 inhibited the proliferation, migration, and invasion of breast cancer cells. Interestingly, transcriptional profiles indicated that genes differentially expressed in response to Amot-p130 knockdown were mostly related to β-catenin signaling in MCF7 cells. More importantly, most of the downstream partners of β-catenin were associated with stemness. In a further validation, Amot-p130 inhibited the cancer stem cell potential of breast cancer cells both in vitro and in vivo. Mechanistically, Amot-p130 decreased β-catenin stability by competing with Axin for binding to tankyrase, leading to a further inhibition of the WNT pathway. In conclusions, Amot-p130 functions as a tumor suppressor gene in breast cancer, disrupting β-catenin stability by competing with Axin for binding to tankyrase. Amot-p130 was identified as a potential target for WNT pathway-targeted therapies in breast cancer.

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“…[ 110 ] AMOTp130 can also modulate the Rho signaling pathway to regulate cell cytoskeletal remodeling, inhibiting breast cancer cell invasion. [ 111 ] Moreover, in NF2 ‐null mesothelioma cells, Motins are stabilized, and knockdown of Motins significantly induces YAP/TAZ activity, cell proliferation, and tumorigenesis. [ 24 ] These findings strongly support the tumor suppressor role of Motins.…”

Section: Motins In Tumorigenesismentioning

confidence: 99%

Angiomotin family proteins in the Hippo signaling pathway

Wang,

2024

BioEssays

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The Motin family proteins (Motins) are a class of scaffolding proteins consisting of Angiomotin (AMOT), AMOT‐like protein 1 (AMOTL1), and AMOT‐like protein 2 (AMOTL2). Motins play a pivotal role in angiogenesis, tumorigenesis, and neurogenesis by modulating multiple cellular signaling pathways. Recent findings indicate that Motins are components of the Hippo pathway, a signaling cascade involved in development and cancer. This review discusses how Motins are integrated into the Hippo signaling network, as either upstream regulators or downstream effectors, to modulate cell proliferation and migration. The repression of YAP/TAZ by Motins contributes to growth inhibition, whereas subcellular localization of Motins and their interactions with actin fibers are critical in regulating cell migration. The net effect of Motins on cell proliferation and migration may contribute to their diverse biological functions.

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AmotP130 regulates Rho GTPase and decreases breast cancer cell mobility

Cited by 7 publications

References 62 publications

Tumor vasculature remolding by thalidomide increases delivery and efficacy of cisplatin

Tumor vasculature remolding by thalidomide increases delivery and efficacy of cisplatin

Angiomotin-p130 inhibits β-catenin stability by competing with Axin for binding to tankyrase in breast cancer

Angiomotin family proteins in the Hippo signaling pathway

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