Snail promotes Cyr61 secretion to prime collective cell migration and form invasive tumor nests in squamous cell carcinoma

Tanaka, Fumi; Rizqiawan, Andra; Higashikawa, Koichiro; Tobiume, Kei; Okui, Gaku; Shigeishi, Hideo; Ono, Shigehiro; Shimasue, Hiroshi; Kamata, Nobuyuki

doi:10.1016/j.canlet.2012.11.023

Cited by 20 publications

(21 citation statements)

References 31 publications

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“…In addition, collective cell migration, which has only recently emerged and is the process whereby cancer cells migrate as a group or as spheres instead of single cells, has been studied in vitro and in vivo . Cells that move in groups, sheets or strands are all connected by cell–cell junctions . Furthermore, collective invasion has been found in histological sections of many cancer types .…”

Section: Introductionmentioning

confidence: 99%

Rab11 collaborates E‐cadherin to promote collective cell migration and indicates a poor prognosis in colorectal carcinoma

Chung

Wei

Hung

et al. 2016

Eur J Clin Investigation

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Section: Introductionmentioning

confidence: 99%

Rab11 collaborates E‐cadherin to promote collective cell migration and indicates a poor prognosis in colorectal carcinoma

Chung

Wei

Hung

et al. 2016

Eur J Clin Investigation

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“…Furthermore, indirect co-culture experiments with trans-well inserts (data not shown), as well as experiments with MSC-derived conditioned media (MSC-CM) (Additional file 2: Figure S2), was not sufficient to induce CCN1 mRNA splicing in INA-6 cells. It has previously been shown that exogenous stimulation using recombinant CCN1 protein induced endogenous CCN1 production [40]. To determine if this effect was mediated through splicing, we investigated if splicing of CCN1 pre-mRNA occurs after treatment with recombinant protein.…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal stem cell contact promotes CCN1 splicing and transcription in myeloma cells

et al. 2014

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CCN family member 1 (CCN1), also known as cysteine-rich angiogenic inducer 61 (CYR61), belongs to the extracellular matrix-associated CCN protein family. The diverse functions of these proteins include regulation of cell migration, adhesion, proliferation, differentiation and survival/apoptosis, induction of angiogenesis and cellular senescence. Their functions are partly overlapping, largely non-redundant, cell-type specific, and depend on the local microenvironment. To elucidate the role of CCN1 in the crosstalk between stromal cells and myeloma cells, we performed co-culture experiments with primary mesenchymal stem cells (MSC) and the interleukin-6 (IL-6)-dependent myeloma cell line INA-6. Here we show that INA-6 cells display increased transcription and induction of splicing of intron-retaining CCN1 pre-mRNA when cultured in contact with MSC. Protein analyses confirmed that INA-6 cells co-cultured with MSC show increased levels of CCN1 protein consistent with the existence of a pre-mature stop codon in intron 1 that abolishes translation of unspliced mRNA. Addition of recombinant CCN1-Fc protein to INA-6 cells was also found to induce splicing of CCN1 pre-mRNA in a concentration-dependent manner. Only full length CCN1-Fc was able to induce mRNA splicing of all introns, whereas truncated recombinant isoforms lacking domain 4 failed to induce intron splicing. Blocking RGD-dependent integrins on INA-6 cells resulted in an inhibition of these splicing events. These findings expand knowledge on splicing of the proangiogenic, matricellular factor CCN1 in the tumor microenvironment. We propose that contact with MSC-derived CCN1 leads to splicing and enhanced transcription of CCN1 which further contributes to the translation of angiogenic factor CCN1 in myeloma cells, supporting tumor viability and myeloma bone disease.

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“…The relative gene expression levels were estimated using the following formula: relative expression = 2 −(Ct [target gene] − Ct[ GAPDH ]) . Table shows the primers we designed according to the previous reports …”

Section: Methodsmentioning

confidence: 99%

“…Table 1 shows the primers we designed according to the previous reports. 15,16 Enzyme-linked immunosorbent assay…”

Section: Rt-pcr and Quantitative Rt-pcrmentioning

confidence: 99%

Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma

et al. 2015

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Tumor-associated macrophages (TAMs) are known to be involved in the progression of various human malignancies. We previously demonstrated that CD204 was a useful marker for TAMs contributing to the angiogenesis, progression, and prognosis of human esophageal squamous cell carcinoma (ESCC). We also showed that conditioned media of ESCC cell lines induced CD204 expression in THP-1 human monocytic leukemia cells. Here, we performed a cDNA microarray analysis between THP-1 cells stimulated with TPA (macrophage [MΦ]-like THP-1 cells) treated with and without conditioned medium of ESCC cell line to clarify the molecular characteristics of TAMs in ESCC. From the microarray data, we discovered that Cyr61 was induced in CD204-positive-differentiated THP-1 cells (TAM-like THP-1 cells). In the ESCC microenvironment, not only cancer cells but also TAMs expressed Cyr61. Interestingly, the expression levels of Cyr61 showed a significant positive correlation with the number of CD204-positive macrophages in ESCCs by immunohistochemistry. Recombinant human Cyr61 (rhCyr61) promoted cell migration and induced the expression of CD204 along with the activation of the MEK/ERK pathway in MΦ-like THP-1 cells. Pretreatment with a MEK1/2 inhibitor significantly inhibited not only the Cyr61-mediated migration but also the CD204 expression in the MΦ-like THP-1 cells. These results suggest that Cyr61 may contribute to the expression of CD204 and the promotion of cell migration via the MEK/ERK pathway in TAMs in the ESCC microenvironment.

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Snail promotes Cyr61 secretion to prime collective cell migration and form invasive tumor nests in squamous cell carcinoma

Cited by 20 publications

References 31 publications

Rab11 collaborates E‐cadherin to promote collective cell migration and indicates a poor prognosis in colorectal carcinoma

Rab11 collaborates E‐cadherin to promote collective cell migration and indicates a poor prognosis in colorectal carcinoma

Mesenchymal stem cell contact promotes CCN1 splicing and transcription in myeloma cells

Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma

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