Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2

Hoffmann, Céline; Mao, Xianqing; Brown-Clay, Joshua D.; Moreau, Flora; Absi, Antoun Al; Wurzer, Hannah; Sousa, Bárbara; Schmitt, Fernando; Berchem, Guy; Janji, Bassam; Thomas, Clément

doi:10.1038/s41598-018-28637-x

Cited by 67 publications

(76 citation statements)

References 48 publications

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“…Surprisingly, hypoxia (24 hours) did not affect invasiveness although previous studies have shown hypoxia to promote the invasiveness of human PCa cells [eg 45,46 ]. Indeed, the effect of hypoxia in promoting cellular invasiveness has been reported also for other cancers, for example colon, 34 breast 47,48 and gastric cancer 49 . The apparent lack of effect in the present study could be due to the “normoxic” Mat‐LyLu cells also having some properties usually associated with hypoxia.…”

Section: Discussioncontrasting

confidence: 71%

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

Rizaner

Uzun

Fraser

et al. 2020

Basic Clin Pharma Tox

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Anti‐invasive effects of riluzole and ranolazine, a neuro‐protectant and an anti‐anginal drug, respectively, on Mat‐LyLu rat prostate cancer (PCa) cells were tested in vitro (a) at non‐toxic doses and (b) under both normoxic and hypoxic conditions, the latter common to growing tumours. Tetrodotoxin (TTX) was used as a positive control. Hypoxia had no effect on cell viability but reduced growth at 48 hours. Riluzole (5 μmol/L) or ranolazine (20 μmol/L) had no effect on cell viability or growth under normoxia or hypoxia over 24 hours. Matrigel invasion was not affected by hypoxia but inhibited by TTX, ranolazine and riluzole under a range of conditions. The expression of Nav1.7 mRNA, the prevailing, pro‐invasive voltage‐gated sodium channel α‐subunit (VGSCα), was up‐regulated by hypoxia. Riluzole had no effect on Nav1.7 mRNA expression in normoxia but significantly reduced it in hypoxia. VGSCα protein expression in plasma membrane was reduced in hypoxia; riluzole increased it but only under hypoxia. It was concluded (a) that riluzole and ranolazine have anti‐invasive effects on rat PCa cells and (b) that Nav1.7 mRNA and protein expression can be modulated by riluzole under hypoxia. Overall, therefore, riluzole and ranolazine may ultimately be “repurposed” as anti‐metastatic drugs against PCa.

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Section: Discussioncontrasting

confidence: 71%

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

Rizaner

Uzun

Fraser

et al. 2020

Basic Clin Pharma Tox

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“…The present study demonstrated that S100A4 protein may be used as a potential biomarker for prognosis in patients with colorectal cancer [38]. The study by Céline Hoffmann et al found that CSRP2 is a novel direct cytoskeletal target of HIF-1 and promotes hypoxicinduced invasion of breast cancer cells by promoting invasive pseudopodia formation [39]. Moreover, another study showed that CXCR4 nuclear localization plays an important role in promoting the metastasis of renal cell carcinoma by facilitating HIF-1α entry into the nucleus [40].…”

Section: Discussionsupporting

confidence: 51%

Development and Validation of a Hypoxia-Related Gene Pairs Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma

Ding

2020

Preprint

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Objective Head and neck squamous cell carcinoma (HNSCC) are a highly aggressive tumor with an extremely poor prognosis. Thus, we aimed to develop and validate a robust prognostic signature that can estimate the prognosis for HNSCC.Methods Data on gene expressions and clinical were downloaded from TCGA and GEO database. To develop the best prognosis signature, a LASSO Cox Regression model was employed. Time-dependent receiver-operating characteristic (ROC) was used to determine the best cut-off value. Patients were divided into high-risk and low-risk hypoxia groups according to cut-off value. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model.Results A 17-HRGPs composed of 24 unique genes was constructed, which was significantly related to OS. In the TCGA and GEO datasets, patients in the high hypoxia risk group have a poor prognosis (TCGA: P < 0.001, GEO: P < 0.05). After adjusting for other clinicopathological parameters, the 17-HRGP signature was independent prognostic factors in patients with HNSCC (P < 0.05). Functional analysis revealed that mRNA binding, gene silencing by RNA, RNA binding involved in posttranscriptional gene silencing signaling pathway were enriched in the low-risk groups. For this model, C-index was 0.684, which was higher than that of many established risk models. Macrophages M0, Mast cells activated, NK cells resting, and T cells CD4 memory resting, etc. were significantly higher in the high-risk group, and B cells memory, Plasma cells, T cells follicular helper, T cells gamma delta, and T cells CD8, etc. were significantly higher in the low-risk group.Conclusion In summary, our study constructed a robust HRGPs signature as molecular markers for predicting the outcome of HNSCC patients.

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“…In particular, the cross-linking with actin cytoskeleton, such as LIM domain protein, can maintain the functional structure of cardiomyocytes by a mechanism involving its own binding and actin filament cross-linking, which plays an important role in the development of heart disease (Hoffmann et al, 2014). In addition, LIM domain proteins have also been reported to be involved in the invasion and metastasis of cancer as components and targets of the cytoskeleton (Hoffmann et al, 2016(Hoffmann et al, , 2018. The PDLIM5 splicing isoforms exhibit tissue-specific expression: the long isoforms are widely expressed in various tissues, while the short isoforms are only highly expressed in cardiac and skeletal muscle (Yamazaki et al, 2010).…”

Section: The Expression Structure and Distribution Of Pdlim5mentioning

confidence: 99%

An Overview of the Cytoskeleton-Associated Role of PDLIM5

Huang

Ouyang

et al. 2020

Front. Physiol.

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Regenerative medicine represented by stem cell technology has become one of the pillar medical technologies for human disease treatment. Cytoskeleton plays important roles in maintaining cell morphology, bearing external forces, and maintaining the effectiveness of cell internal structure, among which cytoskeleton related proteins are involved in and play an indispensable role in the changes of cytoskeleton. PDLIM5 is a cytoskeleton-related protein that, like other cytoskeletal proteins, acts as a binding protein. PDZ and LIM domain 5 (PDLIM5), also known as ENH (Enigma homolog), is a cytoplasmic protein with a molecular mass of about 63 KDa that consists of a PDZ domain at the N-terminus and three LIM domains at the C-terminus. PDLIM5 binds to the cytoskeleton and membrane proteins through its PDZ domain and interacts with various signaling molecules, including protein kinases and transcription factors, through its LIM domain. As a cytoskeleton-related protein, PDLIM5 plays an important role in regulating cell proliferation, differentiation and cell fate decision in multiple tissues and cell types. In this review, we briefly summarize the state of knowledge on the PDLIM5 gene, structural properties, and molecular functional mechanisms of the PDLIM5 protein, and its role in cells, tissues, and organ systems, and describe the possible underlying molecular signaling pathways. In the last part of this review, we will focus on discussing the limitations of existing research and the future prospects of PDLIM5 research in turn.

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Hypoxia promotes breast cancer cell invasion through HIF-1α-mediated up-regulation of the invadopodial actin bundling protein CSRP2

Cited by 67 publications

References 48 publications

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

Development and Validation of a Hypoxia-Related Gene Pairs Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma

An Overview of the Cytoskeleton-Associated Role of PDLIM5

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