Inhibitor of growth 4 is involved in melanomagenesis and induces growth suppression and apoptosis in melanoma cell line M14

Cai, Limin; Li, Xiaomei; Zheng, Shaohua; Wang, Yanhua; Wang, Yandong; Li, Haiyan; Yang, Jing; Sun, Jianfang

doi:10.1097/cmr.0b013e32831bc42f

Cited by 40 publications

(41 citation statements)

References 24 publications

(35 reference statements)

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“…To the best of our knowledge, no study has investigated the level of expression of ING4 in human osteosarcoma tissue as compared with normal bone tissue, or the prognostic value of ING4 expression in patients diagnosed with osteosarcoma. Similar to the results of previous studies regarding other malignant tumors (11,18,20,(28)(29)(30)(31), the results of the present study demonstrated that the osteosarcoma tissues had significantly decreased expression of ING4 when compared with the normal bone tissues (P<0.001). The majority of the osteosarcoma specimens had a score of (-) or (+), whilst no normal bone specimens had a score of (-) or (+).…”

Section: Discussionsupporting

confidence: 82%

“…Previous studies have demonstrated that ING4 expression is suppressed or reduced in a number of malignancies, and the degree of expression is associated with the tumor grade (11,18,20,(28)(29)(30)(31). To the best of our knowledge, no study has investigated the level of expression of ING4 in human osteosarcoma tissue as compared with normal bone tissue, or the prognostic value of ING4 expression in patients diagnosed with osteosarcoma.…”

Section: Discussionmentioning

confidence: 87%

“…ING4 expression is decreased in a number of tumor tissues and the degree of low expression corresponds with tumor grade (11,18,20,(28)(29)(30)(31). Allelic loss and mutation of ING4 have also been observed in various cancer cell lines (26,32,33), thus suggesting that ING4 is a promising tumor suppressor.…”

Section: Introductionmentioning

confidence: 93%

“…Activated caspase-3 disrupts the function of poly(ADP-ribose) polymerase and, as a result, DNA cannot be repaired. Therefore, ING4 may also induce apoptosis through activation of the mitochondrial apoptotic pathway in a p53-independent manner (20)(21)(22). Evidence suggests that ING4 may suppress the expression of the target gene, hypoxia-inducible factor-1α, by interacting with its plant homeodomain finger motif under hypoxic conditions (23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

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Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

et al. 2016

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Abstract. Osteosarcoma is the most prevalent type of primary malignant bone tumor. Inhibitor of growth 4 (ING4) has been demonstrated to function as a tumor suppressor through multiple pathways, and is its expression is understood to be suppressed or reduced in various malignancies. The present study aimed to investigate the expression of ING4 and to determine its prognostic value in osteosarcoma tissue. Formalin-fixed, paraffin-embedded tissue microarrays were analyzed, and contained 41 osteosarcoma specimens and 11 normal bone tissue specimens with duplicate cores. ING4 expression was evaluated by immunohistochemical staining. The association between ING4 expression in the osteosarcoma and normal bone tissues was analyzed, in addition to the association between ING4 expression and Enneking classification of the osteosarcoma tissues. A significant statistical difference was observed in the ING4 immunohistochemical staining score between the osteosarcoma and normal bone tissues (P<0.001). Furthermore, a significant negative correlation was detected between the ING4 immunohistochemical staining scores and the Enneking classification results of the 41 osteosarcoma tissues (P=0.002). Low expression of ING4 was observed in the osteosarcoma specimens, and this reduced expression of ING4 was negatively correlated with Enneking classification. Thus, the results of the present study indicate that ING4 may serve as a promising prognostic marker in osteosarcoma. IntroductionOsteosarcoma, the most common primary bone malignancy, accounts for ~20% of all bone tumors and ~5% of all pediatric tumors (1). Osteosarcoma has an overwhelming tendency for invasion and early metastasis (2). Although treatment with surgery and neoadjuvant chemotherapy appears to cure 60-70% of cases (3), the 5-year survival rate for patients with recurrent and metastatic osteosarcoma is only 20% (4,5). Research investigating the mechanism of osteosarcoma development has primarily focused on chromosomal abnormalities, genetic alterations of tumor suppressor genes, activation of oncogenes and dysregulation of major signaling pathways. However, the molecular events that lead to the development of osteosarcoma are not yet fully understood.Inhibitor of growth 4 (ING4) functions as a tumor suppressor, thus serving an inhibitory role during the generation and development of various types of tumor, including thyroid (6), gastric (7), lung (8) and breast cancer (9). ING4 physically interacts with and phosphorylates p65, a subunit of nuclear factor-κB (NF-κB), therefore suppressing the activity of NF-κB (10). The inhibition of NF-κB negatively regulates various target genes, including matrix metalloproteinase (MMP)-2, MMP-9, interleukin (IL)-6, IL-8, cyclooxygenase-2 and colony stimulating factor-3. The downregulation of these cytokines inhibits angiogenesis and tumor cell growth (11-15). In RKO colorectal cancer cells, ING4 expression was able to decrease the cell population in the S-phase of the cell cycle in a p53-dependent manner, as well as upregulate p21...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

et al. 2016

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“…[5][6][7][8] ING4 can significantly induce tumor growth suppression in different tumor types via induction of cell-cycle alteration and apoptosis and inhibition of tumor angiogenesis by repressing nuclear factor kB and hypoxia-inducible factor-1a activity and consequently reducing production of proangiogenic factors. 5,[9][10][11][12][13][14] ING4 can also enhance chemosensitivity to DNA-damage agents such as doxorubicin and etoposide in HepG2 hepatocarcinoma cells. 10 Furthermore, ING4 can exhibit remarkable inhibitory effect on tumor cell spreading, migration and invasion via colocalization and interaction with liprin a1 at lamellipodia 15 and downregulation of matrix metalloproteinase-2 and matrix metalloproteinase-9.…”

Section: Introductionmentioning

confidence: 99%

Enhanced tumor suppression by an ING4/IL-24 bicistronic adenovirus-mediated gene cotransfer in human non-small cell lung cancer cells

Zhu

Xie

et al. 2011

Cancer Gene Ther

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ING4 as a member of inhibitor of growth (ING) tumor suppressor family has potent inhibitory effects on a variety of tumors. Interleukin-24 (IL-24), a cytokine-tumor suppressor, also shows broad-spectrum and tumor-specific antitumor activities. In this report, we constructed an ING4/IL-24 bicistronic adenovirus (Ad-ING4-IL-24) and assessed its combined effect on in vitro and in vivo A549 human non-small cell lung cancer cells. We demonstrated that ING4 and IL-24 combination treatment by adenovirusmediated ING4 and IL-24 coexpression induced additive growth suppression and apoptosis as well as an overlapping effect on upregulation of P21, P27, Fas, Bax and cleaved Caspases-8, 9, 3 and downregulation of Bcl-2 in in vitro A549 lung carcinoma cells. Moreover, Ad-ING4-IL-24 treatment additively inhibited in vivo A549 lung carcinoma subcutaneous (s.c.) xenografted tumor growth and reduced CD34 and microvessel density in A549 xenografted tumors in athymic nude mice. The enhanced antitumor activity elicited by Ad-ING4-IL-24 was closely associated with the coordinate activation of extrinsic and intrinsic apoptotic pathways and additive inhibition of tumor angiogenesis. Thus, our results indicate that cancer gene therapy combining two or more tumor suppressors such as ING4 and IL-24 may constitute a novel and effective therapeutic strategy for lung carcinoma and other cancers.

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Inhibitor of growth tumor suppressors in cancer progression

Piche¹,

Li²

2010

Cell. Mol. Life Sci.

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The inhibitor of growth (ING) family of tumor suppressors has five members and is implicated in the control of apoptosis, senescence, DNA repair, and cancer progression. However, little is known about ING activity in the regulation of cancer progression. ING members and splice variants seem to behave differently with respect to cancer invasion and metastasis. Interaction with histone trimethylated at lysine 4 (H3K4me3), hypoxia inducible factor-1 (HIF-1), p53, and nuclear factor kappa-B (NF-kappaB) are potential mechanisms by which ING members exert effects on invasion and metastasis. Subcellular mislocalization, rapid protein degradation, and to a lesser extent ING gene mutation are among the mechanisms responsible for inappropriate ING levels in cancer cells. The aim of this review is to summarize the different roles of ING family tumor suppressors in cancer progression and the molecular mechanisms involved.

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Inhibitor of growth 4 is involved in melanomagenesis and induces growth suppression and apoptosis in melanoma cell line M14

Cited by 40 publications

References 24 publications

Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

Enhanced tumor suppression by an ING4/IL-24 bicistronic adenovirus-mediated gene cotransfer in human non-small cell lung cancer cells

Inhibitor of growth tumor suppressors in cancer progression

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