Intermediate Filaments as Potential Target for Cancer 2 Treatment

Strouhalova, Katerina; Přechová, Magdalena; Gandalovičová, Aneta; Brábek, Jan; Gregor, Martin; Rösel, Daniel

doi:10.20944/preprints201912.0253.v1

Cited by 6 publications

(5 citation statements)

References 113 publications

(160 reference statements)

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“…30,35 These include several of the annexins, known markers related to different types of cancer, especially AnnexinA2. 36−38 Also, included among cancer-related proteins are vimentin, 39,40 an important EMT marker and CD29 41,42 also known as integrin beta 1 (ITGB1), which is often associated with aggressive cancers. CD73, also known as NT5E, is involved in cancer-related processes and upregulated in many cancers, making it an important marker for cancer.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

In-Depth Proteome Profiling of Small Extracellular Vesicles Isolated from Cancer Cell Lines and Patient Serum

Abhange,

Kitata,

Zhang

et al. 2023

J. Proteome Res.

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Extracellular vesicle (EV) secretion has been observed in many types of both normal and tumor cells. EVs contain a variety of distinctive cargoes, allowing tumor-derived serum proteins in EVs to act as a minimally invasive method for clinical monitoring. We have undertaken a comprehensive study of the protein content of the EVs from several cancer cell lines using direct data-independent analysis. Several thousand proteins were detected, including many classic EV markers such as CD9, CD81, CD63, TSG101, and Syndecan-1, among others. We detected many distinctive cancer-specific proteins, including several known markers used in cancer detection and monitoring. We further studied the protein content of EVs from patient serum for both normal controls and pancreatic cancer and hepatocellular carcinoma. The EVs for these studies have been isolated by various methods for comparison, including ultracentrifugation and CD9 immunoaffinity column. Typically, 500−1000 proteins were identified, where most of them overlapped with the EV proteins identified from the cell lines studied. We were able to identify many of the cell-line EV protein markers in the serum EVs, in addition to the large numbers of proteins specific to pancreatic and HCC cancers.

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Section: ■ Results and Discussionmentioning

confidence: 99%

In-Depth Proteome Profiling of Small Extracellular Vesicles Isolated from Cancer Cell Lines and Patient Serum

Abhange,

Kitata,

Zhang

et al. 2023

J. Proteome Res.

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“…PLEC is abundant in the two most metastatic cell lines, being very low in MNT1, which may indicate that the intermediate filament may not be linked in the focal adhesion points of MNT1 in the presence of low level of PLEC. This, in turn, could affect the actin migration in the EMT of MNT1 cells (69)(70)(71). Increased differences between pigmented and non-pigmented cell lines were also noted for calpain 2 (CAPN2), aspartate beta-hydroxylase (ASPH) and MYOF.…”

Section: Discussionmentioning

confidence: 99%

New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma

et al. 2023

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Melanoma is a form of skin cancer that can rapidly invade distant organs. A distinctive feature of melanomas is their pigmentation status, as melanin is present in most skin melanomas, whilst many metastatic tumors could become amelanotic. Besides the obvious malfunction of the key genes of the melanin pathway, the amelanotic tumors could bear a characteristic molecular signature accounting for their aggressivity. Using mass spectrometry-based proteomics we report here a distinctive panel of biomarkers for amelanotic aggressive melanoma that differ from the less invasive pigmented cells. The developed method allows the label-free quantification of proteins identified by LC-MS/MS analysis. We found a set of proteins comprising AHNAK, MYOF, ANXA1, CAPN2, ASPH, EPHA2, THBS1, TGM2, ACTN4 along with proteins involved in cell adhesion/migration (integrins, PLEC, FSCN1, FN1) that are highly expressed in amelanotic melanoma. Accompanying the down regulation of pigmentation specific proteins such as tyrosinase and TYRP1, these biomarkers are highly specific for a type of highly invasive melanoma. Interestingly, the LC-MS/MS proteomics analysis in hypoxia revealed that the abundance of this specific set of proteins found in normoxia was rather unaltered in these conditions. These biomarkers could therefore predict a metastatic behaviour for the amelanotic cells in the early stages of the tumor development and thus serve in melanoma prognostic. Applying this algorithm to related databases including melanoma samples published by independent laboratories/public databases we confirm the specificity of the newly found signatures. Overall, we begin to unravel the molecular alterations in the amelanotic melanoma and how basic proteomics offers insights into how to assess the clinical, pathological and misdiagnosis differences between the main subtypes of melanoma.

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“…Interestingly, in advanced melanoma models, TRPV2 also associates with the intermediate filament vimentin network, conceivably in order to extensively regulate cytoskeletal organization and adhesion structures mechanical maturation (27,28). Note that as such, vimentin expression often correlates with tumor aggressiveness (49).…”

Section: Discussionmentioning

confidence: 99%

The mechanosensitive TRPV2 calcium channel controls human melanoma invasiveness and metastatic potential

Shoji

Bayet

Devedec

et al. 2021

Preprint

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Discovery of therapeutic targets against metastasis is of primary importance since being the main cause of cancer-related death. Deregulation of calcium homeostasis has been involved in numerous cellular metastatic behaviors, although the molecular determinants supporting these processes remain often unclear. Here, we showed that the expression of the plasma membrane TRPV2 calcium channel is a prominent feature in melanoma progression and dissemination. In fact, TRPV2 activity was sufficient to confer an invasive phenotype to non-invasive melanoma cells. Conversely, the invasive and migratory potential of highly metastatic melanoma cells was abolished upon TRPV2 silencing. Mechanistically, TRPV2 supports melanoma cells aggressiveness by being a new regulator of the calpain-dependent maturation of focal adhesion, and actin cytoskeleton remodeling. Finally, TRPV2 overexpression is a marker of advanced malignancy and bad prognosis in human melanoma tumor samples. Altogether, TRPV2-induced Ca2+ signaling orchestrates in vitro motility and invasiveness of melanoma cells, as well as in vivo metastatic melanoma tumors dissemination.

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Intermediate Filaments as Potential Target for Cancer 2 Treatment

Cited by 6 publications

References 113 publications

In-Depth Proteome Profiling of Small Extracellular Vesicles Isolated from Cancer Cell Lines and Patient Serum

In-Depth Proteome Profiling of Small Extracellular Vesicles Isolated from Cancer Cell Lines and Patient Serum

New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma

The mechanosensitive TRPV2 calcium channel controls human melanoma invasiveness and metastatic potential

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