Mechanisms of local invasion in enteroendocrine tumors: Identification of novel candidate cytoskeleton-associated proteins in an experimental mouse model by a proteomic approach and validation in human tumors

Couderc, Christophe; Bollard, Julien; Couté, Yohann; Massoma, Patrick; Poncet, Gilles; Lépinasse, Florian; Hervieu, Valérie; Gadot, Nicolas; Sanchez, Jean‐Charles; Scoazec, Jean‐Yves; Diaz, Jean‐Jacques; Roche, Colette

doi:10.1016/j.mce.2014.09.006

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…Interestingly, cytoskeleton dynamic seemed to be altered upon variation of NRP-2 expression. Indeed, the expression of the tubulin stabilizer CRMP2 is increased in shNRP-2 cells, consistent with a previous study of our group showing that CRMP2 protein level was reduced in progressive NET disease [4]. Furthermore, NRP-2 ectopic expression in CNDT2.5 cells decreased the level of the phosphorylated form of cofilin, an actin-binding protein known to regulate the cytoskeleton [22].…”

Section: Discussionsupporting

confidence: 91%

“…Our group previously identified two members of the class 3 semaphorin (SEMA3) signaling pathway namely collapsin response mediator protein‐2 (CRMP2) and semaphorin 3F (SEMA3F) as regulators of SI‐NET invasion and progression . Taking advantage of the model of multiple ileal NETs, we recently demonstrated that promoter methylation induced‐loss of SEMA3F accompanied the progression of ileal NETs, and that reexpression of SEMA3F in preclinical models restricted tumor cell proliferation, thus highlighting the antitumor role of SEMA3F in SI‐NETs .…”

Section: Introductionmentioning

confidence: 99%

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Neuropilin‐2 contributes to tumor progression in preclinical models of small intestinal neuroendocrine tumors

Bollard

Patte

Radkova

et al. 2019

The Journal of Pathology

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The identification of novel regulators of tumor progression is a key challenge to gain knowledge on the biology of small intestinal neuroendocrine tumors (SI‐NETs). We recently identified the loss of the axon guidance protein semaphorin 3F as a protumoral event in SI‐NETs. Interestingly the expression of its receptor neuropilin‐2 (NRP‐2) was still maintained. This study aimed at deciphering the potential role of NRP‐2 as a contributor to SI‐NET progression. The role of NRP‐2 in SI‐NET progression was addressed using an approach integrating human tissue and serum samples, cell lines and in vivo models. Data obtained from human SI‐NET tissues showed that membranous NRP‐2 expression is present in a majority of tumors, and is correlated with invasion, metastatic abilities, and neovascularization. In addition, NRP‐2 soluble isoform was found elevated in serum samples from metastatic patients. In preclinical mouse models of NET progression, NRP‐2 silencing led to a sustained antitumor effect, partly driven by the downregulation of VEGFR2. In contrast, its ectopic expression conferred a gain of aggressiveness, driven by the activation of various oncogenic signaling pathways. Lastly, NRP‐2 inhibition led to a decrease of tumor cell viability, and sensitized to therapeutic agents. Overall, our results point out NRP‐2 as a potential therapeutic target for SI‐NETs, and will foster the development of innovative strategies targeting this receptor. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Neuropilin‐2 contributes to tumor progression in preclinical models of small intestinal neuroendocrine tumors

Bollard

Patte

Radkova

et al. 2019

The Journal of Pathology

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“…CRMP2 was has been shown to play a role in the cell cycle through stabilization of the mitotic apparatus during cell division [17]. Recent data also show a potential role in tumor cell metastasis, as CRMP2 expression was downregulated in late stage invasive tumor cells relative to early stage cells in a small-intestinal neuroendocrine mouse xenograft study [18]. CRMP2 expression is also decreased in breast cancer tissues, suggesting it could function in tumor suppression [19].…”

Section: Resultsmentioning

confidence: 99%

RNA interference-mediated knockdown of SIRT1 and/or SIRT2 in melanoma: Identification of downstream targets by large-scale proteomics analysis

Wilking-Busch

Ndiaye

Liu

et al. 2018

Journal of Proteomics

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Melanoma is the deadliest form of skin cancer, due to its aggressive nature, metastatic potential, and a lack of sufficient treatment options for advanced disease. Therefore, detailed investigations into the molecular mechanisms of melanoma growth and progression are needed. In the search for candidate genes to serve as therapeutic targets, the sirtuins show promise as they have been found to be upregulated in melanoma and they regulate a large number of proteins involved in cellular processes known to affect tumor growth, such as DNA damage repair, cell cycle arrest, and apoptosis. In this study, we used a large-scale label-free comparative proteomics system to identify novel protein targets that are affected following knockdown of SIRT1 and/or 2 in A375 metastatic melanoma cell line. Our study offers important insight into the potential downstream targets of SIRTs 1 and/or 2. This may unravel new potential areas of exploration in melanoma research.

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“…Many proteins involved in dynamic changes in actin cytoskeleton are verified links to the invasive and metastatic phenotypes of malignant cancer cells . As a cytoskeletal protein, MICAL2 was reported to increase oxidative stress and ROS production, which leads to increased cancer cell migratory and invasive capacities .…”

Section: Discussionmentioning

confidence: 99%

MICAL2 promotes breast cancer cell migration by maintaining epidermal growth factor receptor (EGFR) stability and EGFR/P38 signalling activation

et al. 2017

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Mechanisms of local invasion in enteroendocrine tumors: Identification of novel candidate cytoskeleton-associated proteins in an experimental mouse model by a proteomic approach and validation in human tumors

Cited by 5 publications

References 22 publications

Neuropilin‐2 contributes to tumor progression in preclinical models of small intestinal neuroendocrine tumors

Neuropilin‐2 contributes to tumor progression in preclinical models of small intestinal neuroendocrine tumors

RNA interference-mediated knockdown of SIRT1 and/or SIRT2 in melanoma: Identification of downstream targets by large-scale proteomics analysis

MICAL2 promotes breast cancer cell migration by maintaining epidermal growth factor receptor (EGFR) stability and EGFR/P38 signalling activation

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