IGF-1 induces expression of zinc-finger protein 143 in colon cancer cells through phosphatidylinositide 3-kinase and reactive oxygen species

Paek, A Rome; Kim, Seok Hyun; Kim, Sun Shin; Kim, Young Ho; You, Hye Jin

doi:10.3858/emm.2010.42.10.068

Cited by 15 publications

(24 citation statements)

References 24 publications

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“…We therefore presume that the homeobox family TFs highly expressed by idNK cells may contribute to their immaturity. ZNF143 can be induced by IGF‐1 . Interestingly, we previously reported that IGF‐1 is critical for human NK‐cell cytotoxicity , which is consistent with the observed higher Znf143 expression in mpNK cells that are known to exert cytotoxic activity.…”

Section: Discussionsupporting

confidence: 87%

Molecular signatures and transcriptional regulatory networks of human immature decidual NK and mature peripheral NK cells

Wang

Zhou

et al. 2014

Eur J Immunol

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Many differences exist between human immature and mature natural killer (NK) cells, but their respective molecular signatures and transcriptional regulators are relatively unknown. To gain new insights into the diversity and developmental regulation of human NK cells, we used data from high-resolution microarrays with independent verification to describe a comprehensive comparative analysis between immature decidual NK (idNK) cells with a Eur. J. Immunol. 2014. 44: 2771-2784 activity [6,7]. Our previous work showed that most dNK cells belong to the CD27 − CD11b − subset, which has an immature phenotype, displays developmental potential in response to IL-15, and increases cytotoxic potential in response to insulin-like growth factor 1 (IGF-1) [8,9]. Several exogenous cytokines are involved in NK-cell development and function, including IL-2, IL-15, and IL-21, and novel endogenous cytokines have more recently been found, including bone morphogenetic protein 4 (BMP4) and IGF-1 [9][10][11]. Although many transcription factors (TFs) have been identified to affect NK-cell differentiation or function in mice, including ID2, NFIL3 (E4BP4), EOMES, ETS-1, and T-bet, little is known about human NK-cell transcriptional regulators [12][13][14]. Since the molecular signature of NK cells has been well-described in mice [15], we sought to compare the results from mouse models to humans to see if developmental mechanisms are conserved.Using human whole-genome microarray data sets with subsequent verification, we provide novel molecular descriptions for human immature and mature NK cells; most importantly, our findings offer new insights into the transcriptional regulators that govern NK-cell development and function. Our study thus provides a valuable resource for further investigations into NK-cell biology. Results idNK cells exhibit immature characteristics compared with mpNK cellsNK cells in the peripheral blood account for a small fraction of total lymphocytes (ß10%) and are composed of two different subsets: the predominant CD56 dim CD16 + mature subset (ß95%) and the much smaller CD56 bright CD16 − immature subset (ß5%).In contrast, NK cells are the dominant lymphocyte in the decidua during normal pregnancy, comprising up to ß70% of the total lymphocytes and approximately 90% of dNK cells were of the CD56 bright CD16 − immature phenotype [6,16] (Fig. 1A and B, and Supporting Information Fig. 1A and C). T-bet regulates the terminal maturation and function of murine NK cells during the final stage of development [17]. ID2 is expressed in NK-cell progenitors and regulates their early developmental processes [13,18]. To further confirm that dNK cells are more immature than pNK cells, we analyzed T-bet and ID2 expression. Interestingly, we found that dNK cells were mostly T-bet − , while >90% of the pNK cells were T-bet + ( Fig. 1A and B). Additionally, western blot analysis showed that ID2 was exclusively expressed by dNK cells (Fig. 1C). Furthermore, we detected many known cell-surface markers related to NK-cell maturation. C...

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Section: Discussionsupporting

confidence: 87%

Molecular signatures and transcriptional regulatory networks of human immature decidual NK and mature peripheral NK cells

Wang

Zhou

et al. 2014

Eur J Immunol

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“…The control cell lines (HCT116 sh-control) and cell lines stably expressing ZNF143 shRNA (HCT116 sh-ZNF143) or GIPC shRNA (HCT116 sh-GIPC) were selected in 10 μg/ml puromycin dihydrochloride for 2 weeks and maintained in growth medium containing 1 μg/ml puromycin dihydrochloride. To avoid clonal variation, the individual clones for each stable cell line produced by infection were pooled (Choi et al, 2010;Paek et al, 2010).…”

Section: Cell Culturementioning

confidence: 99%

“…ZNF143 has been implicated in DNA-damage responses and the resistance of cancer cells to cisplatin, suggesting that the protein plays a role in carcinogenesis and cancer cell survival (Ishiguchi et al, 2004;Wakasugi et al, 2007). Previously, we showed that IGF-1 induced ZNF143 expression through reactive oxygen species (ROS) and phosphatidylinositide 3-kinase (PI3-kinase)-linked signaling pathways (Paek et al, 2010). However, several questions remain to be answered, such as how IGF-1R induces ZNF143 expression.…”

Section: Introductionmentioning

confidence: 99%

GAIP-Interacting Protein, C-Terminus Is Involved in the Induction of Zinc-Finger Protein 143 in Response to Insulin-like Growth Factor-1 in Colon Cancer Cells

Paek

You

2011

Molecules and Cells

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Previously, we reported that the expression of zinc-finger protein 143 (ZNF143) was induced by insulin-like growth factor-1 (IGF-1) via reactive oxygen species (ROS)- and phosphatidylinositide-3-kinase (PI3-kinase)-linked pathways in colon cancer cells. Here, we investigated whether GAIP-interacting protein, C-terminus (GIPC), a binding partner of IGF-1R, is involved in ZNF143 expression through IGF-1 and IGF-1R signaling in colon cancer cells. The knockdown of GIPC in colon cancer cells reduced ZNF143 expression in response to IGF-1. IGF-1 signaling through its receptor, leading to the phosphorylation and activation of the PI3-kinase-Akt pathway and mitogenactivated protein kinases (MAPKs) was unaffected by the knockdown of GIPC, indicating the independence of the GIPC-linked pathway from PI3-kinase- and MAPK-linked signaling in IGF-1-induced ZNF143 expression. In accordance with previous results in breast cancer cells (Choi et al., 2010), the knockdown of GIPC reduced ROS production in response to IGF-1 in colon cancer cells. Furthermore, the knockdown of GIPC reduced the expression of Rad51, which is regulated by ZNF143, in response to IGF-1 in colon cancer cells. Taken together, these data suggest that GIPC is involved in IGF-1 signaling leading to ZNF143 expression through the regulation of ROS production, which may play a role for colon cancer tumorigenesis.

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“…In humans, ZNF143 has been suggested to play roles in various activities . Previous studies demonstrated that ZNF143 is involved in the cell cycle, cell viability, and drug resistance . Furthermore, the knockdown of ZNF143 expression by small interfering RNA (siRNA) downregulated the expression of various cell cycle/DNA replication‐associated genes and inhibited the progression of the cell cycle and tumor cell growth .…”

mentioning

confidence: 99%

“…(2) Previous studies demonstrated that ZNF143 is involved in the cell cycle, cell viability, and drug resistance. (3)(4)(5)(6)(7)(8)(9)(10)(11) Furthermore, the knockdown of ZNF143 expression by small interfering RNA (siRNA) downregulated the expression of various cell cycle/DNA replication-associated genes and inhibited the progression of the cell cycle and tumor cell growth. (3) ZNF143 was also more strongly expressed in solid tumors than in adjacent non-tumor samples.…”

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confidence: 99%

YPC‐21661 and YPC‐22026, novel small molecules, inhibit ZNF143 activity in vitro and in vivo

et al. 2017

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Zinc‐finger protein 143 (ZNF143) is a transcription factor that is involved in anticancer drug resistance and cancer cell survival. In the present study, we identified a novel small molecule N‐(5‐bromo‐2‐methoxyphenyl)‐3‐(pyridine‐3‐yl) propiolamide (YPC‐21661) that inhibited ZNF143 promoter activity and down‐regulated the expression of the ZNF143‐regulated genes, RAD51, PLK1, and Survivin, by inhibiting the binding of ZNF143 to DNA. In addition, YPC‐21661 was cytotoxic and induced apoptosis in the human colon cancer cell line, HCT116 and human prostate cancer cell line, PC‐3. 2‐(pyridine‐3‐ylethynyl)‐5‐(2‐(trifluoromethoxy)phenyl)‐1,3,4‐oxadiazole (YPC‐22026), a metabolically stable derivative of YPC‐21661, induced tumor regression accompanied by the suppression of ZNF143‐regulated genes in a mouse xenograft model. The present study revealed that the inhibition of ZNF143 activity by small molecules induced tumor regression in vitro and in vivo; therefore, ZNF143 is a promising target of cancer therapeutics.

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IGF-1 induces expression of zinc-finger protein 143 in colon cancer cells through phosphatidylinositide 3-kinase and reactive oxygen species

Cited by 15 publications

References 24 publications

Molecular signatures and transcriptional regulatory networks of human immature decidual NK and mature peripheral NK cells

Molecular signatures and transcriptional regulatory networks of human immature decidual NK and mature peripheral NK cells

GAIP-Interacting Protein, C-Terminus Is Involved in the Induction of Zinc-Finger Protein 143 in Response to Insulin-like Growth Factor-1 in Colon Cancer Cells

YPC‐21661 and YPC‐22026, novel small molecules, inhibit ZNF143 activity in vitro and in vivo

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