CD9 expression in gastric cancer and its significance

Hori, Hiroki; Yano, Shoichiro; Koufuji, Kikuo; Takeda, Jinryo; Shirouzu, Kazuo

doi:10.1016/j.jss.2004.01.014

Cited by 56 publications

(45 citation statements)

References 40 publications

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“…The integrin-binding CD9 tetraspanin protein has been shown to increase cell motility and b1-integrin activity when ectopically expressed in Chinese hamster ovarian (CHO) cells (Kotha et al, 2008). In agreement with our findings, CD9 has been shown to be positively associated with cancer cell invasion in vivo, especially during the process of extravasation through the endothelium (Hori et al, 2004;Sauer et al, 2003).…”

Section: Discussionsupporting

confidence: 88%

A functional genetic screen reveals new regulators of β1-integrin activity

Pellinen

Rantala

Arjonen

et al. 2012

Journal of Cell Science

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Summary b1 integrins constitute a large group of widely distributed adhesion receptors, which regulate the ability of cells to interact with their surroundings. This regulation of the expression and activity of integrins is crucial for tissue homeostasis and development and contributes to inflammation and cancer. We report an RNA interference screen to uncover genes involved in the regulation of b1-integrin activity using cell spot microarray technology in cancer cell lines. Altogether, ten cancer and two normal cell lines were used to identify regulators of b1 integrin activity. Cell biological analysis of the identified b1-integrin regulatory genes revealed that modulation of integrin activity can influence cell invasion in a three-dimensional matrix. We demonstrate with loss-of-function and rescue experiments that CD9 activates and MMP8 inactivates b1 integrins and that both proteins associate with b1 integrins in cells. Furthermore, CD9 and MMP8 regulate cancer cell extravasation in vivo. Our discovery of new regulators of b1-integrin activity highlight the complexity of integrin activity regulation and provide a set of new genes involved in regulation of integrin function.

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Section: Discussionsupporting

confidence: 88%

A functional genetic screen reveals new regulators of β1-integrin activity

Pellinen

Rantala

Arjonen

et al. 2012

Journal of Cell Science

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“…Moreover, CD9 overexpression has been reported in aggressive gastric carcinomas (Hori et al, 2004) and high-grade astrocytic tumors (Kawashima et al, 2002). Therefore, CD9 could be required for the invasive growth of TGCTs.…”

Section: Role Of Ddx1 In Testicular Tumorigenesismentioning

confidence: 99%

DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes

et al. 2009

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Cytogenetic analysis has identified 12p gain as the most frequent abnormality in human testicular germ cell tumors (TGCTs). It has been suggested that amplification and overexpression of stem cell-associated genes, including cyclin-D2, on the human chromosome 12p region are involved in germ cell tumorigenesis. By subtractive cDNA analysis, we identified Ddx1, a member of the DEAD-box protein family, as a gene predominantly expressed in the primordial germ cells of mouse embryos. Knockdown of Ddx1 in a mouse spermatogonia-derived cell line, GC-1spg, by short interference RNA repressed the expression of cyclin-D2, CD9 and GDF3 genes. In the mouse cyclin-D2 gene, a genomic DNA region between À348 and À329 was responsible for transcriptional activation by DDX1 based on reporter and gel shift assays. Similarly, DDX1 knockdown in the human TGCT cell line NEC8 repressed the expression of stem cell-associated genes localized on chromosome 12p13.3, including cyclin-D2, CD9 and NANOG. DDX1-knockeddown TGCT cells could not form solid tumors in nude mice. Furthermore, in situ hybridization revealed that DDX1 mRNA was produced in both seminoma and nonseminoma types of human TGCT samples. We conclude that DDX1 is a critical factor for testicular tumorigenesis.

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“…CD9 is involved in cell proliferation (16). Its overexpression has not been previously associated with ovarian carcinoma, although it has been described as a possible marker for gastric cancer (17). Notably, CD9 underexpression has been associated with ovarian tumor progression (18).…”

Section: Primary and Cultured Hose Are Distinguishable Bymentioning

confidence: 99%