S100A11 promotes cell proliferation via P38/MAPK signaling pathway in intrahepatic cholangiocarcinoma

Zhang, Meixia; Gan, Wei; Jing, Chuyu; Zheng, Su-Su; Yi, Yong; Zhang, Juan; Xu, Xiaowu; Lin, Jiajia; Zhang, Bo‐heng; Qiu, Shuang–Jian

doi:10.1002/mc.22903

Cited by 19 publications

(10 citation statements)

References 31 publications

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“…As the heatmap shows, the key genes related to the MAPK signaling pathway were significantly upregulated, while FoxA2 expression was significantly decreased in FoxA2 -/- mice. As previous reports showed, the MAPK signaling pathway extensively participates in cell proliferation and differentiation and is related to tumor prognosis including in intrahepatic cholangiocarcinoma [28–30]. Consistently, the results of the IHC analysis suggested that the expression of key mediators in the MAPK signaling pathway, such as p-ERK1/2 and RAS, was significantly increased.…”

Section: Discussionsupporting

confidence: 80%

Loss of FoxA2 accelerates neoplastic changes in the intrahepatic bile duct partly via the MAPK signaling pathway

Shen

Zhou

Zhang

et al. 2019

Aging

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Background: Intrahepatic cholangiocarcinoma (ICC) is characterized by a highly aggressive nature and a dismal outcome. FOXA2 is an archetypal transcription factor involved in cholangiocyte proliferation.Results: FOXA2 expression was negatively correlated with tumor stage (p = 0.024). Univariate and multivariate analyses showed that low FoxA2 expression was associated with tumor relapse and survival. At 20 weeks after TAA administration, FoxA2-/- mice displayed significant manifestations of neoplasia, while WT mice did not.RNA sequencing analysis showed that the expression of genes in the MAPK signaling pathway was significantly higher in FoxA2-/- mice. IHC and Western blot results showed that p-ERK1/2, CREB1 and RAS were highly expressed in FoxA2-/- mice. Furthermore, using in vitro experiments with siRNA, we found that low expression of FoxA2 could exacerbate the metastatic potential of ICC. The expression of p-ERK1/2 and RAS, which are key mediators of the MAPK signaling pathway, was significantly increased.Conclusion: Low FOXA2 expression negatively affected the prognosis of patients with ICC. Loss of FoxA2 expression could promote intrahepatic bile duct neoplasia partly via activation of the MAPK signaling pathway.Materials and methods: In all, the data of 85 patients with ICC were retrospectively collected and analyzed. TAA was used to induce ICC in FoxA2-/- mice and WT mice. RNA-sequencing analysis was used to identify the expression of different genes.

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Section: Discussionsupporting

confidence: 80%

Loss of FoxA2 accelerates neoplastic changes in the intrahepatic bile duct partly via the MAPK signaling pathway

Shen

Zhou

Zhang

et al. 2019

Aging

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“…The return to normal values of S10AB under treatment is also consistent with our previous finding of a dramatic increase in this protein’s abundance specifically observed in neoplastic vs. preneoplastic rat mesothelial cells [ 15 ]. The comparable S10AB values observed in curcumin-treated and normal rats lead to the conclusion that the activation of different signaling pathways, which were associated with S10AB increases in different types of cancer [ 38 , 39 , 40 , 41 ], was cancelled under treatment. Finally, we found the same opposite evolution of S10A4 and S10A8 as that observed in oral squamous cell carcinomas, suggesting that combinatorial analysis of these two S100 proteins would predict the lesions’ degree of malignancy [ 42 ].…”

Section: Discussionmentioning

confidence: 86%

Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas

Pouliquen

Boissard

Henry

et al. 2020

Cancers

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Investigations of liver metastatic colonization suggest that the microenvironment is preordained to be intrinsically hospitable to the invasive cancer cells. To identify molecular determinants of that organotropism and potential therapeutic targets, we conducted proteomic analyses of the liver in an aggressive model of sarcomatoid peritoneal mesothelioma (M5-T1). The quantitative changes between SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra) proteotype patterns of the liver from normal rats (G1), adjacent non-tumorous liver from untreated tumor-bearing rats (G2), and liver from curcumin-treated rats without hepatic metastases (G3) were compared. The results identified 12 biomarkers of raised immune response against M5-T1 cells in G3 and 179 liver biomarker changes in (G2 vs. G1) and (G3 vs. G2) but not in (G3 vs. G1). Cross-comparing these 179 candidates with proteins showing abundance changes related to increasing invasiveness in four different rat mesothelioma tumor models identified seven biomarkers specific to the M5-T1 tumor. Finally, analysis of correlations between these seven biomarkers, purine nucleoside phosphorylase being the main biomarker of immune response, and the 179 previously identified proteins revealed a network orchestrating liver colonization and treatment efficacy. These results highlight the links between potential targets, raising interesting prospects for optimizing therapies against highly invasive cancer cells exhibiting a sarcomatoid phenotype and sarcoma cells.

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“…For example, Wang et al, clari ed that TSPAN1 was involved in CCA progression via PI3K/AKT pathway [41]. Zhang et al, suggested that S100A11 promoted cell proliferation by p38/MAPK signaling pathway in iCCA [42]. This study discovered that GSG2 knockdown contributed to downregulation of P-Akt, CCND1, PIK3CA, and upregulation of MAPK9.…”

Section: Discussionmentioning

confidence: 76%

GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration

Zhou¹,

Huang

Nie

et al. 2020

Preprint

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Background: Cholangiocarcinoma (CCA) is the second most common type of hepatocellular carcinoma with high aggressiveness and extremely poor prognosis. Homo sapiens germ cell associated 2 (GSG2) is a histone H3 threonine-3 kinase required for normal mitosis. Nevertheless, the role and mechanism of GSG2 in progression and development of CCA remain elusive. Methods: In the present study, correlation between GSG2 and CCA was elaborated by IHC, Mann-Whitney U and Spearman grading correlation. GSG2 knockdown cell lines were successfully constructed and further used to construct mouse xenotransplantation models. Subsequently, cell proliferation, cell apoptosis, cell cycle and cell migration were detected by MTT assay, Flow Cytometry and wound-healing assay, respectively. Results: It was demonstrated that GSG2 was overexpressed in CCA specimens and relevant cell lines. The statistical analysis determined that high GSG2 expression was positively associated with more advanced tumor grade. Importantly, GSG2 knockdown inhibited cell proliferation, migration, promoted cell apoptosis and arrested cell cycle in G2 phase. Meanwhile, in vivo results also supported that GSG2 knockdown inhibit tumor growth. Additionally, GSG2 was involved in CCA progression via suppressing EMT. Conclusions: In summary, our findings suggested that GSG2 may be a potential therapeutic target for CCA patients.

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S100A11 promotes cell proliferation via P38/MAPK signaling pathway in intrahepatic cholangiocarcinoma

Cited by 19 publications

References 31 publications

Loss of FoxA2 accelerates neoplastic changes in the intrahepatic bile duct partly via the MAPK signaling pathway

Loss of FoxA2 accelerates neoplastic changes in the intrahepatic bile duct partly via the MAPK signaling pathway

Curcumin Treatment Identifies Therapeutic Targets within Biomarkers of Liver Colonization by Highly Invasive Mesothelioma Cells—Potential Links with Sarcomas

GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration

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