MDA-9/Syntenin: An emerging global molecular target regulating cancer invasion and metastasis

Das, Swadesh K.; Sarkar, Devanand; Emdad, Luni; Fisher, Paul B.

doi:10.1016/bs.acr.2019.03.011

Cited by 20 publications

(32 citation statements)

References 194 publications

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“…Therefore, both GTPases are required for the generation of a specific subpopulation of EVs with enhanced pro-metastatic properties and further work is needed to fully unravel the downstream molecular pathways. With this work, RalA and RalB add to the list of proteins known to control exosome secretion and to affect tumor progression, such as Rab27a (Bobrie et al, 2012;Kren et al, 2020;Peinado et al, 2012), Alix (Monypenny et al, 2018), syntenin (Das et al, 2019) and components of the ESCRT machinery (Mattissek and Teis, 2014). These studies demonstrate that the number of EVs secreted by a primary tumor is an essential element determining the efficiency of metastasis.…”

Section: Discussionmentioning

confidence: 89%

Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes

Ghoroghi

Mary

Larnicol

et al. 2021

eLife

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Cancer extracellular vesicles (EVs) shuttle at distance and fertilize pre-metastatic niches facilitating subsequent seeding by tumor cells. However, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Using mouse models, we show that GTPases of the Ral family control, through the phospholipase D1, multi-vesicular bodies homeostasis and tune the biogenesis and secretion of pro-metastatic EVs. Importantly, EVs from RalA or RalB depleted cells have limited organotropic capacities in vivoand are less efficient in promoting metastasis. RalA and RalB reduce the EV levels of the adhesion molecule MCAM/CD146, which favors EV-mediated metastasis by allowing EVs targeting to the lungs. Finally, RalA, RalB, and MCAM/CD146, are factors of poor prognosis in breast cancer patients. Altogether, our study identifies RalGTPases as central molecules linking the mechanisms of EVs secretion and cargo loading to their capacity to disseminate and induce pre-metastatic niches in a CD146-dependent manner.

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Section: Discussionmentioning

confidence: 89%

Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes

Ghoroghi

Mary

Larnicol

et al. 2021

eLife

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“…GBM accounts for the majority of brain tumors with a poor patient prognosis, despite current interventional therapeutic strategies (surgery, radiation, and/or chemotherapy) (1)(2)(3)(4)(5). In principle, defining promising GBM-specific therapeutic targets could serve as a basis for developing strategies to advance effective therapies for GBM by elucidating the molecular pathways involved in gliomagenesis (2)(3)(4)(5). Heat shock proteins (HSPs) provide a primary protein signature for GBM progression serving as a nexus for ECM remodeling and EMT (6).…”

Section: Resultsmentioning

confidence: 99%

“…glioblastoma | HSPB1 | Fli-1 | radioresistance | TMZ resistance M ajor pathological features that impose impediments to the management of glioblastoma (GBM) include infiltrative growth behavior, intratumoral heterogeneity, and propensity for tumor recurrence (1)(2)(3)(4)(5). Conventional approaches using radiation and temozolomide (TMZ; chemotherapy) have proven unsuccessful in treating GBM because of acquired therapeutic resistance and eventual disease recurrence.…”

mentioning

confidence: 99%

“…Conventional approaches using radiation and temozolomide (TMZ; chemotherapy) have proven unsuccessful in treating GBM because of acquired therapeutic resistance and eventual disease recurrence. Unraveling the molecular mechanisms involved in GBM development and progression provide a potential path forward for developing effective GBM therapies (1,3,5). Omics studies in GBM have reported elevated expression of heat shock proteins (HSPs) (1, 6) that promote tumor growth by activating GBM cell proliferation and inhibiting death pathways (1).…”

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confidence: 99%

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Lumefantrine, an antimalarial drug, reverses radiation and temozolomide resistance in glioblastoma

Rajesh

Biswas

Kumar

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Glioblastoma multiforme (GBM) is an aggressive cancer without currently effective therapies. Radiation and temozolomide (radio/TMZ) resistance are major contributors to cancer recurrence and failed GBM therapy. Heat shock proteins (HSPs), through regulation of extracellular matrix (ECM) remodeling and epithelial mesenchymal transition (EMT), provide mechanistic pathways contributing to the development of GBM and radio/TMZ-resistant GBM. The Friend leukemia integration 1 (Fli-1) signaling network has been implicated in oncogenesis in GBM, making it an appealing target for advancing novel therapeutics. Fli-1 is linked to oncogenic transformation with up-regulation in radio/TMZ-resistant GBM, transcriptionally regulating HSPB1. This link led us to search for targeted molecules that inhibit Fli-1. Expression screening for Fli-1 inhibitors identified lumefantrine, an antimalarial drug, as a probable Fli-1 inhibitor. Docking and isothermal calorimetry titration confirmed interaction between lumefantrine and Fli-1. Lumefantrine promoted growth suppression and apoptosis in vitro in parental and radio/TMZ-resistant GBM and inhibited tumor growth without toxicity in vivo in U87MG GBM and radio/TMZ-resistant GBM orthotopic tumor models. These data reveal that lumefantrine, an FDA-approved drug, represents a potential GBM therapeutic that functions through inhibition of the Fli-1/HSPB1/EMT/ECM remodeling protein networks.

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“…Blood vessels are a crucial provider of nutrients, signaling highways and avenues for tumoral metastasis (44)(45)(46)(47)(48)(49). This makes them a prime target for many therapies including PDT, as their destruction or normalization has been correlated with reductions in tumor volume (50).…”

Section: Monitoring Changes In Tumor Vasculature Post-pdtmentioning

confidence: 99%

Role of Ultrasound and Photoacoustic Imaging in Photodynamic Therapy for Cancer

Hester

Kuriakose

Nguyen

et al. 2020

Photochem & Photobiology

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Photodynamic therapy (PDT) is a phototoxic treatment with high spatial and temporal control and has shown tremendous promise in the management of cancer due to its high efficacy and minimal side effects. PDT efficacy is dictated by a complex relationship between dosimetry parameters such as the concentration of the photosensitizer at the tumor site, its spatial localization (intracellular or extracellular), light dose and distribution, oxygen distribution and concentration, and the heterogeneity of the inter‐ and intratumoral microenvironment. Studying and characterizing these parameters, along with monitoring tumor heterogeneity pre‐ and post‐PDT, provides essential data for predicting therapeutic response and the design of subsequent therapies. In this review, we elucidate the role of ultrasound (US) and photoacoustic imaging in improving PDT‐mediated outcomes in cancer—from tracking photosensitizer uptake and vascular destruction, to measuring oxygenation dynamics and the overall evaluation of tumor responses. We also present recent advances in multifunctional theranostic nanomaterials that can improve either US or photoacoustic imaging contrast, as well as deliver photosensitizers specifically to tumors. Given the wide availability, low‐cost, portability and nonionizing nature of US and photoacoustic imaging, together with their capabilities of providing multiparametric morphological and functional information, these technologies are thusly inimitable when deployed in conjunction with PDT.

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MDA-9/Syntenin: An emerging global molecular target regulating cancer invasion and metastasis

Cited by 20 publications

References 194 publications

Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes

Ral GTPases promote breast cancer metastasis by controlling biogenesis and organ targeting of exosomes

Lumefantrine, an antimalarial drug, reverses radiation and temozolomide resistance in glioblastoma

Role of Ultrasound and Photoacoustic Imaging in Photodynamic Therapy for Cancer

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