Stromal fibroblasts in the microenvironment of gastric carcinomas promote tumor metastasis via upregulating TAGLN expression

Yu, Beiqin; Chen, Xuehua; Li, Jianfang; Qu, Ying; Peng, Yibing; Huang, Jian; Yan, Jun; Yu, Yingyan; Gu, Qinxuan; Zhu, Zhenggang; Liu, Bingya

doi:10.1186/1471-2121-14-17

Cited by 57 publications

(56 citation statements)

References 34 publications

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“…Fibroblasts are known to express transgelin (53) and Schwann cells also express transgelin based on our data (Fig. 3C), indicating that two of the major cells forming MPNST tumors, Schwann cells and fibroblasts, express transgelin.…”

Section: Discussionsupporting

confidence: 56%

TAGLN expression is upregulated in NF1-associated malignant peripheral nerve sheath tumors by hypomethylation in its promoter and subpromoter regions

et al. 2014

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Neurofibromatosis type 1 (NF1) caused by NF1 gene mutation is a commonly inherited autosomal dominant disorder. Malignant peripheral nerve sheath tumors (MPNSTs), a type of aggressive sarcoma, are a major cause of mortality in NF1 patients. The malignant transformation of benign plexiform neurofibromas (PNs) to MPNSTs is a marked peculiarity in NF1 patients, yet the pathogenesis remains poorly understood. We found that an actin-associated protein transgelin (SM22) was highly expressed in NF1-deficient MPNST tissues compared to NF1-deficient PN tissues using immunohistological staining and primary cultured MPNST cells in western blot analysis. We further found that this transgelin upregulation was caused by increased transcriptional expression of the TAGLN gene encoding transgelin. Comparison of DNA methylation values in the promoter and subpromoter regions of the TAGLN gene in three types of NF1-deficient primary-cultured cells, derived from an NF1 patient’s normal phenotype, a benign PN and MPNST tissues, revealed that the TAGLN gene was hypomethylated in the MPNST cells. Next, to determine the functional role of transgelin in MPNST pathogenesis, we manipulated the TAGLN gene expression and investigated the alteration of the RAS-mitogen-activated protein kinase (MAPK) signaling pathway in the normal-phenotypic and malignant tumor cells. The downregulation of TAGLN expression in NF1-deficient MPNST tumor cells through the treatment of the small interfering RNA resulted in a decrease in the RAS activation (GTP-RAS) and the downstream ERK1/2 activation (phosphorylated ERK1/2), while the overexpression of TAGLN in normal-phenotypic NF1-deficient cells caused an increase in RAS and ERK1/2 activation. These results indicate that upregulation of transgelin caused by hypomethylation of the TAGLN gene is closely involved in tumor progression in NF1.

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Section: Discussionsupporting

confidence: 56%

TAGLN expression is upregulated in NF1-associated malignant peripheral nerve sheath tumors by hypomethylation in its promoter and subpromoter regions

et al. 2014

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“…The ECM proteins secreted by CAFs provide an optimal microenvironment for gastric cancer. Furthermore, a multitude of molecules, including growth, transcription and inflammatory factors, are also highly expressed in CAFs and stimulate the invasion of gastric cancer cells; these include fibroblast growth factor 9 (67), Twist 1 (68), interleukin 22 (69), galectin-1 (70) and transgelin (71). Consequently, CAFs, as important components of stromal cells, secrete numerous molecules that further promote tumourigenesis.…”

Section: Promotion Of Metastasis By Cafmentioning

confidence: 99%

Mechanisms of peritoneal dissemination in gastric cancer (Review)

2017

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Abstract. Peritoneal dissemination is the most frequent metastatic pattern of gastric cancer, but the mechanisms underlying peritoneal dissemination are yet to be elucidated. Paget's 'seed and soil' hypothesis is recognized as the fundamental theory of metastasis. The 'seeding' theory proposes that the formation of peritoneal dissemination is a multistep process, including detachment from the primary tumour, transmigration and attachment to the distant peritoneum, invasion into subperitoneal tissue and proliferation with blood vascular neogenesis. In the present review, the progress of each step is discussed. Milky spots, as a lymphatic apparatus, are indicative of lymphatic orifices on the surface of the peritoneum. These stomata are open gates for peritoneal-free cancer cells to migrate into the submesothelial space. Therefore, milky spots provide suitable 'soil' for cancer cells to implant. Other theories have also been proposed to clarify the peritoneal dissemination process, including the transvessel metastasis theory, which suggests that the peritoneal metastasis of gastric cancer develops via a vascular network mediated by hypoxia inducible factor-1α.

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“…Furthermore, the prevalence of CAFs is related to certain clinicopathologic features, such as tumor size and invasive depth, as well as metastasis of gastric carcinoma [13]. Moreover, CAFs could stimulate tumor cell growth, migration and invasion, as well as resistance to chemotherapy [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐106b in cancer‐associated fibroblasts from gastric cancer promotes cell migration and invasion by targeting PTEN

Yang

Chen

et al. 2014

FEBS Letters

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Edited by Varda Rotter Keywords:Cancer associated fibroblasts microRNA Protein tyrosine phosphatase and tensin homologue Gastric cancer a b s t r a c t It is well established that the interaction between cancer cells and microenvironment has a critical role in tumor development, but the roles of miRNAs in this interaction are rarely known. Here, we have shown that miR-106b is up-regulated in cancer associated fibroblasts compared with normal fibroblasts established from patients with gastric cancer, the expression level of miR-106b is associated with poor prognosis of patients, and CAFs with down-regulated miR-106b could significantly inhibit gastric cancer cell migration and invasion by targeting PTEN. Taken together, these data suggest that miR-106b might be a novel candidate target for the treatment of gastric cancer.

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Stromal fibroblasts in the microenvironment of gastric carcinomas promote tumor metastasis via upregulating TAGLN expression

Cited by 57 publications

References 34 publications

TAGLN expression is upregulated in NF1-associated malignant peripheral nerve sheath tumors by hypomethylation in its promoter and subpromoter regions

TAGLN expression is upregulated in NF1-associated malignant peripheral nerve sheath tumors by hypomethylation in its promoter and subpromoter regions

Mechanisms of peritoneal dissemination in gastric cancer (Review)

MicroRNA‐106b in cancer‐associated fibroblasts from gastric cancer promotes cell migration and invasion by targeting PTEN

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