S100A8 and S100A9 Are Associated with Colorectal Carcinoma Progression and Contribute to Colorectal Carcinoma Cell Survival and Migration via Wnt/β-Catenin Pathway

Duan, Liang; Wu, Rui; Ye, Liwei; Wang, Haiyan; Xia, Yang; Zhang, Yunyuan; Chen, Xian; Zuo, Guo‐Wei; Zhang, Yan; Weng, Yaguang; Luo, Jinyong; Tang, Min; Shi, Qiong; He, Tong‐Chuan; Zhou, Lan

doi:10.1371/journal.pone.0062092

Cited by 78 publications

(79 citation statements)

References 68 publications

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“…A further study reported that S100A8 and S100A9 contribute to colorectal carcinoma cell survival and migration via the Wnt/β-catenin pathway. S100A8 and S100A9 increase total β-catenin levels and promote transcription of its target genes (c-myc and MMP7), resulting in the upregulation of the Wnt/β-catenin pathway (24). The present study confirmed that S100A8 and S100A9 is vital for the migration of CNE1 NPC cells, and indicated that MMP7 may be involved.…”

Section: Discussionsupporting

confidence: 79%

“…At 48 h and 72 h, after the effects of the siRNAs had diminished, cell migration in the S100A8 and S100A9 siRNA-transfected experimental groups were restored to a certain degree, while scratched areas in the blank control, negative control and mock-treatment groups had filled with cells. At each time-point after scratching (24,48 and 72 h), the migration ratio of the S100A8 and S100A9 siRNA-transfected experimental groups was significantly lower compared with that of the blank control, negative control and mock-treatment groups (Tables III and IV). No significant differences were observed among the blank control, negative control and mock-treatment groups (P>0.05; Fig.…”

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confidence: 94%

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Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells

et al. 2015

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Abstract. The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells.

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Section: Discussionsupporting

confidence: 79%

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confidence: 94%

Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells

et al. 2015

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“…Increasing evidence indicates that the expression of S100A8 is increased in CRC tissues and the elevated expression of S100A8 is associated not only with histological differentiation, but also with Dukes' stage and lymph node metastasis in CRC (9). In the present study, we found that S100A8 promoted the expression of miR-155 and the secretion of IL-1β and TNF-α through activation of the NF-κB signaling pathway in macrophages, eventually facilitating the migration of CRC cells, which occurred in the inflammation environment mimicked by LPS.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that S100A8 plays an important role in regulating tissue inflammation as a ligand of toll-like receptor 4 (TLR4) and/or receptor for advanced glycation end products (RAGE) (7,8). Aberrant expression of S100A8 has been found in different types of tumors including CRC (9) and the accumulation of S100A8 positive cells is always located in the invasive margin of colorectal carcinoma (10) which plays a critical role in the tumor microenvironment. Interestingly, mounting evidence indicates that the apical surface of the intestinal epithelium is exposed to lipopolysaccharides (LPS) from the lumen due to intestinal mucosal permeability and bacterial translocation (11).…”

Section: Introductionmentioning

confidence: 99%

S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment

Zha

Sun

et al. 2016

Oncology Reports

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Abstract.Previous studies have shown that S100 calcium-binding protein A8 (S100A8) contributes to the survival and migration of colorectal cancer (CRC) cells. However, whether S100A8 participates in the progression and metastasis of CRC via the regulation of macrophages in the tumor inflammatory microenvironment remains unknown. In this study, phorbol myristate acetate (PMA) was used to induce the differentiation of THP-1 monocytes to macrophages. MTT assay, western blot analysis, immunofluorescence staining, semi-quantitative RT-PCR (semi-PCR), quantitative real-time PCR (qPCR), Gaussia luciferase activity assay and ELISA were performed to analyze the roles and molecular mechanisms of S100A8 in the modulation of macrophages. MTT assay, flow cytometric analysis, Hoechst staining, wound healing and Transwell migration assay were used to test the effect of S100A8 on the viability and migration of CRC cells co-cultured with macrophages in the inflammatory microenvironment. We found that THP-1 monocytes were induced by PMA and differentiated to macrophages. S100A8 activated the NF-κB pathway in the macrophages and promoted the expression of miR-155 and inflammatory cytokines IL-1β and TNF-α in the inflammatory microenvironment mimicked by lipopolysaccharides (LPS). Furthermore, S100A8 contributed to augment the migration but not the viability of the CRC cells co-cultured with the macrophages in the inflammatory microenvironment. Altogether, our study demonstrated that S100A8 facilitated the migration of CRC cells in the inflammatory microenvironment, and the underlying molecular mechanisms may be partially attributed to the overexpression of miR-155, IL-1β and TNF-α through activation of the NF-κB pathway in macrophages. IntroductionColorectal cancer (CRC), for which distant metastasis accounts for the leading cause of cancer mortality, is one of the most malignant gastrointestinal carcinomas worldwide (1). The pathogenesis of CRC is a complex process and involves environmental influences, genetic alterations, and the host immune system and their interactions. The formation of an inflammatory microenvironment also plays a pivotal role in the development of CRC (2). The host microenvironment is comprised of numerous infiltrating immune cell types and resident tumor cells. Among the immune cells, macrophages play an indispensable role. For instance, macrophage infiltration in colon tissue has been observed in both inflammatory bowel disease (IBD) and CRC (4), and the cytokines secreted by macrophages under certain conditions have directly or indirectly stimulated inflammation and tumor progression (5,6). Although great progress has been made, the interactions and the molecular mechanisms between CRC and the inflammatory microenvironment remain unknown. S100A8 (calgranulin A or S100 calcium-binding protein A8) is a member of the low-molecular calcium binding S100 protein family. It also belongs to the family of damage-associated molecular patterns (DAMPs). Studies have shown that S100A8 plays an important role in regul...

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“…As an inflammatory protein, it may serve a role in tumor-stromal interactions (14), and elevated levels of protein S100-A8 have been observed in numerous types of malignancy, including cutaneous squamous cell carcinoma (12), gastric adenocarcinoma (15) and kidney cancer (16). In addition, a previous study demonstrated a correlation between the expression levels of protein S100-A8 and colorectal carcinoma progression, during which this protein may contribute to colorectal carcinoma cell survival and migration via the Wnt/β catenin signaling pathway (17). To the best of our knowledge, the present study is the first to report differences in the expression levels of protein S100-A8 between fresh PBT and fresh PMLN tissues, screened using the iTRAQ proteomic technique.…”

Section: Introductionmentioning

confidence: 49%

Protein S100-A8: A potential metastasis-associated protein for breast cancer determined via iTRAQ quantitative proteomic and clinicopathological analysis

Zhong

Kang

et al. 2018

Oncol Lett

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Abstract. Breast cancer is the most common malignancy in females, with metastasis of this type of cancer frequently proving lethal. However, there are still no effective biomarkers to predict breast cancer metastasis. The aim of the present study was, therefore, to analyze breast cancer metastasis-associated proteins and evaluate the association between protein S100-A8 and the prognosis of breast cancer. The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic technique was used to analyze the differential expression of proteins between fresh primary breast tumor (PBT) tissue and fresh paired metastatic lymph nodes (PMLN) tissue. Subsequently, immunohistochemical staining was used to locate and assess the expression of protein S100-A8 in benign breast disease (n=15), primary breast cancer with (n=109) or without (n=83) metastasis, and in paired metastatic lymph nodes (n=109) formalin fixed paraffin embedded (FFPE) tissue. Staining scores were evaluated and the association between protein S100-A8 expression levels and the clinicopathological characteristics of 192 patients with breast cancer were evaluated using the χ 2 test. Kaplan-Meier and Cox hazards regression analyses were utilized to investigate the association between the expression of protein S100-A8 and the prognosis of patients with breast cancer. A total of 4,837 proteins were identified using the iTRAQ proteomic technique. Among these proteins, 643 differentially expressed proteins were revealed. Protein S100-A8 expression levels were identified to differ between PBT and PMLN tissues. Immunohistochemical staining suggested a significant difference between NMBT and PMLN (P=0.002), and also between PBT and PMLN (P<0.001). Cox hazards regression model analyses suggested that histological grade (P=0.031) and nodal status (P=0.001) were risk factors for lymph nodes metastasis of breast cancer. Kaplan-Meier analyses revealed no significant relationship between protein S100-A8 expression level and overall survival rate of patients with breast cancer. In conclusion, by using the iTRAQ proteomic technique and immunohistochemistry staining, it was identified that protein S100-A8 may be associated with lymph nodes metastasis of breast cancer and be a marker for progression of breast cancer. IntroductionBreast cancer is the most common malignancy and second leading cause of cancer-associated mortality in females globally (1,2). Breast cancer incidence and mortality rates are high in western countries, while the incidence of breast cancer exhibits an increasing trend in developing countries (1). In China in 2010, there were 208,000 cases of breast cancer, with 55,500 mortalities (3,4). The staging of breast cancer is based on the tumor-node-metastasis system, and distinct stages of disease are associated with various prognosis (5). Tumor size and axillary node status are considered risk factors for breast cancer distant metastases (5), whereas the status of regional lymph nodes is critical in defining the staging, treatment and prognosis of brea...

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S100A8 and S100A9 Are Associated with Colorectal Carcinoma Progression and Contribute to Colorectal Carcinoma Cell Survival and Migration via Wnt/β-Catenin Pathway

Cited by 78 publications

References 68 publications

Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells

Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells

S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment

Protein S100-A8: A potential metastasis-associated protein for breast cancer determined via iTRAQ quantitative proteomic and clinicopathological analysis

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