The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression

Atlasi, Yaser; Noori, Rubina; Marolin, Ivana; Franken, Patrick; Brandão, Joana Maia; Biermann, Katharina; Collini, Paola; Grigorian, Mariam; Lukanidin, Eugene; Ambartsumian, Noona; Fodde, Riccardo

doi:10.1016/j.ejca.2016.09.012

Cited by 12 publications

(10 citation statements)

References 44 publications

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“…Recent researchers have identified S100A4 as a tumor metastasis-associated protein in many cancer, such as breast cancer 24 , ovarian cancer 25 , colorectal cancer 26 , lung cancer 27 ,et.al. In our previous studies, S100A4 was identified as a protein that was associated with development and tumor progression of colorectal cancer 20 .…”

Section: Discussionmentioning

confidence: 99%

S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition

Li¹,

Shi²,

Xu³

et al. 2018

J. Cancer

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Driver genes conducing to peritoneal metastasis in advanced gastric cancer remain to be clarified. S100A4 is suggested to evolve in metastasis of gastrointestinal cancer, we aim to explore the role of S100A4 plays in metastasis of advanced gastric cancer and the potential mechanism. Transfection of siRNA or cDNA was applied to alter the expression of protein S100A4 and MYH9, investigation of the expression of epithelial and mesenchymal transition (EMT) associated markers was followed. Cell migration assay was used to screen the alteration of migration ability regulated by S100A4 and MYH9. IHC analysis for tissue sample microarray was performed to reveal their relationship with clinical pathological parameters and potential capacity of predicting survival. Consistent overexpression of S100A4 and MYH9 were found in peritoneal metastasis and primary site compared with adjacent normal tissue. Low expression of S100A4 led to increased epithelial markers as wells as decline of mesenchymal makers, while overexpression of S100A4 led to inverse impact. S100A4 expression was closely correlated with increased migration ability and EMT process induced by TGF-β stimulation. Interference of S100A4 led to downregulation of MYH9 and inactivation of Smad pathway through participating in EMT process, which could be reversed by overexpression of MYH9. Moreover, co-expression of S100A4 and MYH9 was identified in tissue microarray and confirmed by immunofluorescence assay. In conclusion, overexpression of S100A4 and downstream molecular MYH9 in advanced gastric cancer predicted poor prognosis; oncogene S100A4 facilitate EMT process induced by TGF-β stimulation, suggesting a potential target in management of peritoneal metastasis of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition

Li¹,

Shi²,

Xu³

et al. 2018

J. Cancer

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“…CRC development and progression involve a sequential multi-step, multi-stage, and multi-gene mutation process [ 93 ]. Although, S100A4 is not necessary for CRC initiation, its expression was found to be depleted in CRC patients with targeted mutations of the APC or Smad4 gene [ 94 ]. S100A4 gene was modified by a gain-of-function (GOF) mutation in the wingless-type MMTV integration site family (Wnt) signaling pathway and the Wnt activity was observed to have changed in most of CRCs [ 54 ].…”

Section: Introductionmentioning

confidence: 99%

S100A4 in cancer progression and metastasis: A systematic review

et al. 2017

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Metastasis is the leading cause of cancer-related death and directly associates with cancer progression, resistance to anticancer therapy, and poor patient survival. Current efforts focusing on the underlying molecular mechanisms of cancer metastasis attract a special attention to cancer researchers. The epithelial-mesenchymal transition is a complex of molecular program during embryogenesis, inflammation, tissue fibrosis, and cancer progression and metastasis. S100A4, an important member of S100 family proteins, functions to increase the tumor progression and metastasis. The molecular mechanisms of S100A4 involving in the progression and metastasis are diverse in various malignant tumors. Detection of S100A4 expression becomes a promising candidate biomarker in cancer early diagnosis and prediction of cancer metastasis and therefore, S100A4 may be a therapeutic target. This review summarized up to date advancement on the role of S100A4 in human cancer development, progression, and metastasis and the underlying molecular events and then strategies to target S100A4 expression experimentally.

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“… 34 , 35 A role for S100A4 in tumor onset in intestinal tumors was also investigated using genetic ablation or overexpression. 36 That later study concluded that S100A4 does not affect tumor initiation in the intestinal tract but confirmed the role of S100A4 in tumor metastasis. Therefore, the role of S100A4 and S100A4 + cells in tumor onset remains an important unanswered question.…”

Section: Discussionmentioning

confidence: 90%

Depletion of S100A4+ stromal cells does not prevent HCC development but reduces the stem cell-like phenotype of the tumors

et al. 2018

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There is a pressing need for the development of novel approaches to treat and prevent hepatocellular carcinoma (HCC). The S100 calcium-binding protein S100A4 is associated with poor prognosis and metastasis in several human cancers. In addition, a role for S100A4 in modulating cancer-initiating cells stemness properties was recently proposed in head and neck and gastric cancers. Whether S100A4+ stromal cells contribute to tumor onset remains, however, an unanswered question. To address that question, we generated a new mouse model allowing for the depletion of S100A4+ cells in a mouse model of HCC with stemness properties, by crossing mice with hepatic deletion of phosphatase and tensin homolog (PTEN) with mice expressing viral thymidine kinase under the control of S100A4 promoter. Depletion of S100A4+ cells by ganciclovir injection did not prevent the development of HCC but reduced the stemness phenotype of the tumor as measured by the expression of progenitor cell, biliary cell and hepatocyte markers. The results were further confirmed by histology analysis showing reduction of cholangiolar tumor components and degree of oval cell hyperplasia in the adjacent liver. Depletion of S100A4+ cells had also some beneficial effect on the underlying liver disease with a reduction of NAS score, largely due to the reduction of inflammation. In conclusion, this study demonstrated that S100A4+ cells do not contribute to HCC onset but maintain the stemness phenotype of the tumor. This study also suggests for the first time a crosstalk between inflammation and stemness.

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The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression

Cited by 12 publications

References 44 publications

S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition

S100A4-MYH9 Axis Promote Migration and Invasion of Gastric Cancer Cells by Inducing TGF-β-Mediated Epithelial-Mesenchymal Transition

S100A4 in cancer progression and metastasis: A systematic review

Depletion of S100A4+ stromal cells does not prevent HCC development but reduces the stem cell-like phenotype of the tumors

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