Clinicopathological and prognostic significance of S100A4 overexpression in colorectal cancer: a meta-analysis

Liu, Yanqiong; Tang, Weizhong; Wang, Jian; Xie, Li; Li, Taijie; He, Yu; Qin, Xue; Li, Shan

doi:10.1186/1746-1596-8-181

Cited by 28 publications

(30 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 , 37 To further investigate the kinetics of S100A4 + cells during CRC development, which could not be studied using clinical samples, C57 BL/6 mice were administered AOM/DSS (Fig. 1A) that has been used to induce a two-stage carcinogenesis model for CRC.…”

Section: Resultsmentioning

confidence: 99%

“…33 High S100A4 levels in colorectal tumors are associated with metastasis, poor prognosis, and shortened patient survival times. 34 Recently, we found S100A4 promotes colitis development by enhancing host adhesion and colonization of Citrobacter rodentium through the S100A4-mediated host inflammatory responses. 35 Given the importance of S100A4 in tumor biology and inflammation, we questioned whether S100A4 contributes to inflammation-related colon tumorigenesis.…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Zhang

Hou

et al. 2018

OncoImmunology

View full text Add to dashboard Cite

S100A4 plays important roles in tumor development and metastasis, but its role in regulating inflammation and colitis-associated tumorigenesis has not been well characterized. Here, we report that S100A4 expression was increased in azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorectal cancer (CRC) in mice. After AOM/DSS treatment, both S100A4-TK mice with the selective depletion of S100A4-expressing cells and S100A4-deficient (S100A4−/−) mice developed fewer and smaller tumors than wild-type (WT) control littermates. Furthermore, S100A4−/− mice were resistant to DSS-induced colitis, reduced infiltration of macrophages, and the diminished production of proinflammatory cytokines. Further studies revealed that reduced colon inflammation and colorectal tumor development in S100A4−/− mice were partly due to the dampening of nuclear factor (NF)-κB activation in macrophages. Furthermore, the administration of a neutralizing S100A4 antibody to WT mice significantly decreased AOM/DSS-induced colon inflammation and tumorigenesis. These results indicate that S100A4 amplifies an inflammatory microenvironment that promotes colon tumorigenesis and provides a promising therapeutic strategy for treatment of inflammatory bowel disease and prevention of colitis-associated colorectal carcinogenesis.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Zhang

Hou

et al. 2018

OncoImmunology

View full text Add to dashboard Cite

show abstract

“…We speculate that by binding to TG2, S100A4 could potentiate integrin-mediated signaling, and thus enhance cell adhesion and migration, leading to increased metastasis in tumors in which both proteins are overexpressed and released to the ECM. Indeed, both TG2 and S100A4 were found to contribute to the high metastatic properties of several cancers, such as breast and colorectal tumors [42][43][44][45]. It cannot be ruled out that TG2 and S100A4 also interact inside tumor cells (as they both have important intracellular functions) or other cell types as well, and either by cross-linking activity of TG2 or additional protein-protein interactions contribute to the pathomechanism of various tumors.…”

Section: Discussionmentioning

confidence: 99%

Metastasis-associated S100A4 is a specific amine donor and an activity-independent binding partner of transglutaminase-2

Biri

Kiss

Király

et al. 2015

Biochemical Journal

View full text Add to dashboard Cite

Transglutaminase-2 (TG2) is best known as a Ca 2+ -dependent cross-linking enzyme; however, some of its extracellular matrix-related functions are independent from its catalytic activity and include matrix remodeling, adhesion and migration. S100A4 belongs to the Ca 2+ -binding EF-hand S100 protein family and acts both intra-and extracellularly through binding to various partners. It regulates cell migration and its overexpression is strongly associated with metastasis and poor survival in various cancers. TG2 has recently been suggested to mediate S100A4-dependent tumor cell migration. Here we provide evidence that S100A4 is an interacting partner and also specific amine donor of TG2. TG2 incorporates a glutamine donor peptide to Lys100 in the C-terminal random coil region of S100A4. Importantly, the enzyme activity is not necessary for the interaction: S100A4 also binds to TG2 in the presence of a specific inhibitor that keeps the enzyme in an open conformation, or to an enzymatically inactive mutant. We also found that S100A4 considerably enhances TG2-mediated adhesion of A431 epithelial carcinoma cells to the extracellular matrix. This role is independent of enzyme activity and requires the open conformation of TG2. We propose that S100A4 stabilizes the open conformation of TG2, which binds to its cell surface receptor in this state and increases cell adhesion.Summary: S100A4 and transglutaminase-2 have a role in metastasis. S100A4 is an interaction partner and specific amine substrate of transglutaminase-2, promoting its open conformation and leading to enhanced cell adhesion. Studying their interaction could contribute to the better understanding of metastasis.Running title: S100A4: substrate and binding partner of transglutaminase-2

show abstract

“…However, the rate is decreased (<50%) in stage III CRC with lymph node metastasis (3).It is well established that the most frequent cause of treatment failure and high mortality rates is distant metastasis (stage IV)(4).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Expressionof S100a4 and Cd24 in Colorectal Adenoma and Carcinoma.

Ibrahim¹

2016

IJAR

View full text Add to dashboard Cite

Background:-Colorectal carcinoma (CRC) is a major cause of morbidity and mortality worldwide. Both calcium-binding protein, S100A4, and the cell adhesion molecule, CD24, have been implicated to play an important role in carcinogenesis and tumor progression in various human malignancies. Aim:-To evaluate the expressionof S100A4 and CD24 in colorectal tumors and their role in development and progression of CRC and correlate their expression with the clinicopathological features. Methods:-S100A4 and CD24 expression was analyzed by immunohistochemistry in paraffin-embedded specimens of colorectal adenomas (n=18) and CRC (n=40). Results:-S100A4 and CD24 expression was detected in 28/40 (70%) and 24/40 (60%) of CRC respectively.The positive expression rates of S100A4 and CD24 were significantly higher in CRC than adenomas (P<0.05). S100A4 was significantly expressed in tumors with high histological grades (P= 0.03).A statistically significant relationship was found between S100A4 and CD24 expression and advanced tumor stage (P= 0.009 and =0.03), lymph node metastasis (P=0.04 and =0.0001) and lymph-vascular space invasion (LVSI) (P=0.02 and =0.008) respectively, but not with the age, gender and tumor size (P>0.05). Conclusion:-S100A4 and CD24 up-regulation may be associated with the development and progression of CRC. Combined detection of S100A4 and CD24 may serve as an indicator of the aggressive behavior and poor prognosis of CRC.

show abstract

Clinicopathological and prognostic significance of S100A4 overexpression in colorectal cancer: a meta-analysis

Cited by 28 publications

References 48 publications

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Metastasis-associated S100A4 is a specific amine donor and an activity-independent binding partner of transglutaminase-2

Immunohistochemical Expressionof S100a4 and Cd24 in Colorectal Adenoma and Carcinoma.

Contact Info

Product

Resources

About