Vimentin Is Required for Lung Adenocarcinoma Metastasis via Heterotypic Tumor Cell–Cancer-Associated Fibroblast Interactions during Collective Invasion

Richardson, Alessandra M.; Havel, Lauren S.; Koyen, Allyson; Konen, Jessica; Shupe, John; Wiles, Walter Guy; Martin, William; Grossniklaus, Hans E.; Sica, Gabriel L.; Gilbert‐Ross, Melissa; Marcus, Adam I.

doi:10.1158/1078-0432.ccr-17-1776

Cited by 191 publications

(156 citation statements)

References 48 publications

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“…As reported, depletion of N-cadherin suppressed cell invasion and migration in LUAD [29]. As a biomarker of EMT, Vimentin is an intermediate filament protein that plays a role in cell migration to keep structure and motility [30]. Through maintaining heterotypic cancer cell-cancer-associated fibroblast interactions during collective invasion, Vimentin was required for LUAD metastasis [30].…”

Section: Discussionmentioning

confidence: 78%

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

et al. 2020

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Lung adenocarcinoma (LUAD) accounts for ~40% of lung cancer cases, and the 5‐year relative survival rate is no more than 1%. Dysregulation of components of striatin‐interacting phosphatase and kinase (STRIPAK) complexes is associated with various diseases, including cancer. Striatin‐interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth and migration. Here, we investigated the role of STRIP2 in LUAD growth, migration and the underlying mechanisms. Analysis of data from The Cancer Genome Atlas database revealed that STRIP2 is highly expressed and predicted poor outcomes in patients with LUAD. Moreover, quantitative RT‐PCR (qRT‐PCR) analysis revealed that the mRNA expression of STRIP2 is greater in all tested LUAD cells than in a normal lung cell line. To investigate the function of STRIP2, we overexpressed STRIP2 in SPC‐A1 cells and depleted STRIP2 in Calu‐3 cells. Cell proliferation was evaluated by Cell Counting Kit‐8 and colony‐forming assays, and Transwell assay was employed to test cell invasion and migration. Our results indicate that STRIP2 depletion suppressed cell proliferation, invasion and migration in Calu‐3 cells, and overexpression of STRIP2 had the opposite effects in SPC‐A1 cells. Moreover, we discovered that STRIP2 depletion reduced the protein levels of p‐Akt and phosphorylated‐mammalian target of rapamycin (p‐mTOR) in Calu‐3 cells, whereas STRIP2 overexpression increased levels of these proteins in SPC‐A1 cells. Furthermore, we found that silencing of STRIP2 clearly enhanced protein levels of E‐cadherin and reduced levels of N‐cadherin, Vimentin and matrix metalloproteinase‐9 in Calu‐3 cells, whereas overexpression of STRIP2 had the opposite effect in SPC‐A1 cells. Our data indicate that STRIP2 promotes the proliferation and motility of LUAD cells, and this may be mediated through the regulation of the Akt/mTOR pathway and epithelial–mesenchymal transition. These results may facilitate the development of therapeutic strategies to treat LUAD.

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Section: Discussionmentioning

confidence: 78%

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

et al. 2020

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“…In 3D in vitro invasion assays, the addition of CAFs to lung adenocarcinoma cell line spheroids increased spheroid branching. The knock-down of vimentin in CAFs decreased this effect, meaning that the presence of CAFs with intact vimentin led to effective collective migration [97]. This highlights the importance of vimentin in other cell types associated with tumors and metastases and the variety of roles vimentin plays in metastasis formation.…”

Section: Research Focused On Vimentin In Metastasesmentioning

confidence: 83%

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

Strouhalova

Přechová

Gandalovičová

et al. 2020

Cancers

185

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Intermediate filaments constitute the third component of the cellular skeleton. Unlike actin and microtubule cytoskeletons, the intermediate filaments are composed of a wide variety of structurally related proteins showing distinct expression patterns in tissues and cell types. Changes in the expression patterns of intermediate filaments are often associated with cancer progression; in particular with phenotypes leading to increased cellular migration and invasion. In this review we will describe the role of vimentin intermediate filaments in cancer cell migration, cell adhesion structures, and metastasis formation. The potential for targeting vimentin in cancer treatment and the development of drugs targeting vimentin will be reviewed.

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“…However, many recent studies have shown that EMT activation is detrimental to the dissemination and invasion of certain cancer cells . During EMT, epithelial tumor cells lose their epithelial traits, such as E‐cadherin expression, and instead display mesenchymal traits, such as vimentin expression . E‐cadherin is considered to be an active suppressor of the invasion and growth of many epithelial cancers, while higher expression of claudin‐1 is a good prognostic factor in NSCLC, but only in the SCC subgroup .…”

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA linc01433 promotes migration and invasion in non‐small cell lung cancer

et al. 2018

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BackgroundFor many years, lung cancer has been the most common and deadly cancer worldwide. Early diagnosis of non‐small cell lung cancer (NSCLC) in particular is very difficult because the symptoms are often ignored. The five‐year survival rate is very low despite great improvements to therapy. Thus, there is an urgent need to identify prognostic biomarkers and target molecules for the clinical diagnosis and individualized treatment of NSCLC.MethodsWe performed quantitative real‐time PCR to determine the expression levels of the long non‐coding RNA (lncRNA) linc01433 in NSCLC and normal matched lung tissue. Subsequently, we established cell lines with overexpression or knockdown of linc01433 to evaluate the effects on proliferation and metastasis in vitro. Epithelial‐to‐mesenchymal transition was examined using Western blot.ResultsLinc01433 was significantly overexpressed in NSCLC tissues compared to normal lung tissues. In addition, linc01433 levels were associated with smoking history. Linc01433 overexpression in lung cancer cells increased proliferation, migration, and invasion abilities, as well as epithelial‐to‐mesenchymal transition.ConclusionsLinc01433 is a cancer‐related lncRNA that may have an oncogene‐like effect in NSCLC.

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Vimentin Is Required for Lung Adenocarcinoma Metastasis via Heterotypic Tumor Cell–Cancer-Associated Fibroblast Interactions during Collective Invasion

Cited by 191 publications

References 48 publications

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

Vimentin Intermediate Filaments as Potential Target for Cancer Treatment

Long non‐coding RNA linc01433 promotes migration and invasion in non‐small cell lung cancer

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