Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma

Guo, Xinfeng; Liu, W; Pan, Yu; Ni, Peihong; Ji, Jun; Guo, Lei; Zhang, Jian; Wu, Jianlin; Jiang, Junwei; Chen, X; Cai, Qing; Li, Jiong; Gu, Qinxuan; Liu, B; Zhu, Zhenggang; Yu, Yingyan

doi:10.1038/onc.2010.143

Cited by 77 publications

(89 citation statements)

References 51 publications

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“…IRX1 was reported to be downregulated in HNSCC and gastric cancer, and it inhibited cancer cell growth, invasion, and tumorigenesis. (6,7). However, we show here that IRX1 is overexpressed in metastatic osteosarcoma and that it functions as a prometastatic gene, suggesting that IRX1 might play dual roles in cancer development.…”

Section: Nf-κb Pathway Activation Is Involved In Irx1/cxcl14-induced mentioning

confidence: 59%

“…Indeed, IRX2 can be converted from a repressor to an activator after being phosphorylated by FGF8/MAPK signaling (48). In gastric cancer, IRX1 was identified as a transcriptional repressor that could downregulate the expression of a set of tumor-promoting genes such as BDKRB2, FGF7, and HIST2H2BE and thereby inhibit angiogenesis, cell proliferation, and invasion (6). We also found in the present study that IRX1 acted as a transcriptional activator to promote the expression of prometastatic genes like CXCL14 to facilitate osteosarcoma metastasis.…”

Section: Nf-κb Pathway Activation Is Involved In Irx1/cxcl14-induced mentioning

confidence: 99%

“…Recently, IRX1 was identified as a potential tumor-suppressor gene in head and neck squamous cell carcinoma (HNSCC) and gastric cancer (6,7); however, further efforts are required to determine the exact function of IRX1 in the development of other cancers, including osteosarcoma. IRX1 is involved in limb development (8) and the etiology of kyphoscoliosis (9), suggesting that aberrant IRX1 expression may contribute to abnormal bone formation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling

Lu¹,

Song²,

Tang³

et al. 2015

J. Clin. Invest.

111

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Section: Nf-κb Pathway Activation Is Involved In Irx1/cxcl14-induced mentioning

confidence: 59%

Section: Nf-κb Pathway Activation Is Involved In Irx1/cxcl14-induced mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling

Lu¹,

Song²,

Tang³

et al. 2015

J. Clin. Invest.

111

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“…16 These data suggest that Iro genes may play a tumor suppressor role in Drosophila. Moreover, loss or reduced expression of members of Irx gene family are associated with several types of human cancer [44][45][46][47] and, accordingly, they are considered Tumor Suppressor genes (TSGs). The presence of IRO-box and CBD in Irx proteins allows us to hypothesize that Irx proteins may act as TSG by restricting cell Figure 3.…”

Section: Integrating Cell Cycle Control By Iro Proteins In Current Momentioning

confidence: 99%

Expanding the Iroquois genes repertoire: a non-transcriptional function in cell cycle progression

Barrios

Campuzano

2015

Fly

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“…Human gastric cancer cell line, SGC-7901, and human embryonic kidney cell line, HEK293T, which have been characterized previously, 13,20 were grown in RPMI-1640 or Dulbecco's Modified Eagle's Medium (Sigma-Aldrich,St Louis, MI) supplemented with 10% fetal bovine serum (FBS). For experiments, cells originally seeded at 2 Â 10 5 cells/ml were incubated with etoposide (0, 30 lM, 50 lM; BIOMOL, Plymouth, PA), SP600125 (20 lM; Sigma-Aldrich), alone or in combination.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Knockdown of metallopanstimulin‐1 inhibits NF‐κB signaling at different levels: The role of apoptosis induction of gastric cancer cells

Yang

Zhang

et al. 2011

Intl Journal of Cancer

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The ribosomal protein S27 (metallopanstimulin-1, MPS-1) has been reported to be a multifunctional protein, with increased expression in a number of cancers. We reported previously that MPS-1 was highly expressed in human gastric cancer. Knockdown of MPS-1 led to spontaneous apoptosis and repressed proliferation of human gastric cancer cells in vitro and in vivo. However, how does MPS-1 regulate these processes is unclear. Here we performed microarray and pathway analyses to investigate possible pathways involved in MPS-1 knockdown-induced apoptosis in gastric cancer cells. Our results showed that knockdown of MPS-1 inhibited NF-jB activity by reducing phosphorylation of p65 at Ser536 and IjBa at Ser32, inhibiting NF-jB nuclear translocation, and down-regulating its DNA binding activity. Furthermore, data-mining the Gene-RegulatoryNetwork revealed that growth arrest DNA damage inducible gene 45b (Gadd45b), a direct NF-jB target gene, played a critical role in MPS-1 knockdown-induced apoptosis. Over-expression of Gadd45b inhibited MPS-1 knockdown-induced apoptosis via inhibition of JNK phosphorylation. Taken together, these data revealed a novel pathway, the MPS-1/NF-jB/Gadd45b signal pathway, played an important role in MPS-1 knockdown-induced apoptosis of gastric cancer cells. This study sheds new light on the role of MPS-1/NF-jB in apoptosis and the possible use of MPS-1 targeting strategy in the treatment of gastric cancer.Gastric cancer is one of the most common cancers worldwide and it has the second highest mortality rate among all cancers.1 Although combination therapies are commonly used, the outcome of gastric cancer remains poor as the precise molecular events responsible for its generation and progression are still unknown. 2 In our previous studies, we used serological analysis of recombinant cDNA expression libraries (SEREX) to define new gastric cancer-related antigens and we successfully identified an array of relevant proteins, including metallopanstimulin-1 (MPS-1), 3 plant homeodomain finger 10 (PHF10) 4 and frizzled-related protein (FRZB). 5The MPS-1 protein, also known as ribosomal protein S27 (RPS27), is a component of the 40S subunit of the ribosome and belongs to the S27E family of ribosomal proteins.6 Being a zinc finger protein of C4 type, MPS-1 locates both in the cytoplasm and the nucleus. Previous studies demonstrated that MPS-1 is highly expressed in many types of malignant tumors and might be involved in the malignant progression. [7][8][9][10] In addition, the level of MPS-1 protein was found to be elevated in the sera of patients with various types of cancers and it was studied as a tumor marker or tumor-associated antigen;11,12 yet, the role of MPS-1 in tumorigenesis is unclear. We reported previously that the expression of MPS-1 was significantly higher in gastric cancer cells than their normal counterparts. Down-regulation of MPS-1 by shRNAs in gastric cancer cell line SGC-7901 increased spontaneous apoptosis and inhibited the tumor growth in vitro and in vivo.13 However, how do...

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Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma

Cited by 77 publications

References 51 publications

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling

Expanding the Iroquois genes repertoire: a non-transcriptional function in cell cycle progression

Knockdown of metallopanstimulin‐1 inhibits NF‐κB signaling at different levels: The role of apoptosis induction of gastric cancer cells

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