Identification of midkine as a mediator for intercellular transfer of drug resistance

Mirkin, Bernard L.; Clark, Sandra; Zheng, Xin; Chu, Frances; White, Bryan D.; Greene, Mark E.; Rebbaa, Abdelhadi

doi:10.1038/sj.onc.1208671

Cited by 71 publications

(64 citation statements)

References 35 publications

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“…Our data indicated that ACSL5 induces MDK expression and concomitantly promotes cell cycle arrest at the G1 phase, especially under extracellular acidosis (Supplementary Figure 2c). It was recently reported that MDK overexpression also promotes cell cycle arrest at the G1 phase (Mirkin et al, 2005). These observations suggest that cell cycle arrest caused by the ACSL5-induced MDK could be important for survival under stress conditions.…”

Section: Selective Induction Of Mdk Gene By Acsl5 Under Low Ph Conditmentioning

confidence: 77%

“…MDK also confers chemotherapy resistance to cancer cells (Mirkin et al, 2005). Considering the multiple functions of this growth factor, ACSL5-dependent expression of MDK may have a function not only in cell survival under acidosis but also in other malignant phenotypes of cancer cells.…”

Section: Selective Induction Of Mdk Gene By Acsl5 Under Low Ph Conditmentioning

confidence: 99%

“…MDK shows highly increased expression in a number of malignant tumors (Nakagawara et al, 1995;O'Brien et al, 1996;Mishima et al, 1997;Ye et al, 1999;Ikematsu et al, 2000;Jia et al, 2007;Maeda et al, 2007) and enhances tumor progression by promoting survival, growth, migration and angiogenic activity Takei et al, 2001;Kadomatsu and Muramatsu, 2004;Mirkin et al, 2005;Tong et al, 2007). In human brain tumors, especially MDK is overexpressed during tumor progression, and patients whose tumors express a higher level of MDK have a worse prognosis (Mishima et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

Mashima

Sato²,

Sugimoto

et al. 2008

Oncogene

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Extracellular acidosis (low pH) is a tumor microenvironmental stressor that has a critical function in the malignant progression and metastatic dissemination of tumors. To survive under stress conditions, tumor cells must evolve resistance to stress-induced toxicity. AcylCoA synthetase 5 (ACSL5) is a member of the ACS family, which converts fatty acid to acyl-CoA. ACSL5 is frequently overexpressed in malignant glioma, whereas its functional significance is still unknown. Using retrovirusmediated stable gene transfer (gain of function) and small interfering RNA-mediated gene silencing (loss of function), we show here that ACSL5 selectively promotes human glioma cell survival under extracellular acidosis. ACSL5 enhanced cell survival through its ACS catalytic activity. To clarify the genome-wide changes in cell signaling pathways by ACSL5, we performed cDNA microarray analysis and identified an ACSL5-dependent gene expression signature. The analysis revealed that ACSL5 was critical to the expression of tumor-related factors including midkine (MDK), a heparin-binding growth factor frequently overexpressed in cancer. Knockdown of MDK expression significantly attenuated ACSL5-mediated survival under acidic state. These results indicate that ACSL5 is a critical factor for survival of glioma cells under acidic tumor microenvironment, thus providing novel molecular basis for cancer therapy.

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Section: Selective Induction Of Mdk Gene By Acsl5 Under Low Ph Conditmentioning

confidence: 77%

Section: Selective Induction Of Mdk Gene By Acsl5 Under Low Ph Conditmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

Mashima

Sato²,

Sugimoto

et al. 2008

Oncogene

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“…In the present study, we show that the exogenously transfected ALK in 32D cells is constitutively activated by endogenous ligand, the MK protein (Figures 2-4) and that endogenous MK is required for the activation of mitogenic and survival pathways in these cells. Interestingly, recent studies have revealed that the antiapoptotic activity of MK reduces the sensitivity of cells to cytotoxic drugs used clinically and may thus participate in the development of resistance to chemotherapy (Mirkin et al, 2005). This type of autocrine stimulation was extensively studied for EGF and IGF-1 receptor-mediated biological functions (Maheshwari et al, 2001;Scharf and Braulke, 2003;Singh and Harris, 2005) and is now also extended to the ALK receptor.…”

Section: Discussionmentioning

confidence: 99%

Recruitment of insulin receptor substrate-1 and activation of NF-κB essential for midkine growth signaling through anaplastic lymphoma kinase

et al. 2006

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Anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase in the insulin receptor superfamily. We recently demonstrated that the growth factors pleiotrophin (PTN) and midkine (MK) are ligands for ALK and that upon ALK activation, insulin receptor substrate-1 (IRS-1) and other substrates are phosphorylated. Here, the role of IRS-1 in ligand-mediated ALK signaling is investigated in interleukin-3 (IL-3)-dependent 32D murine myeloid cells. These cells do not express ALK and IRS family members, and do not respond to exogenously added PTN or MK. We show that expression of ALK plus IRS-1 renders these cells independent of IL-3 owing to the activation of ALK by endogenous MK. Mutational analysis reveals that this transformed phenotype of 32D cells requires kinase-active ALK as well as the interaction of ALK with IRS-1. Furthermore, 32D/ IRS-1/ALK cells display an enhanced activation of mitogen-activated protein kinase and PI3-kinase pathways, and a selective transcriptional activation of nuclear factor (NF)-jB. Small interfering RNA-mediated knockdown of the endogenous MK or p65/NF-jB revealed that both these are rate limiting for the transformed phenotype induced by ALK plus IRS-1. We conclude that the recruitment of IRS-1 to activated ALK and the activation of NF-jB are essential for the autocrine growth and survival signaling of MK.

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“…MK, a heparin-binding developmentally regulated growth factor, has been reported to promote the survival, growth and migration of many cell types, including neuronal cells, endothelial cells and leukocytes [22,42] . Some studies show that MK functions by promoting S-phase progression and inhibiting apoptosis [43] . We demonstrate that MK promotes the growth of ESCs by preventing apoptosis and inducing the G 1 -S phase transition.…”

Section: Discussionmentioning

confidence: 99%

Promotion of self-renewal of embryonic stem cells by midkine

Yao

Tan

et al. 2010

Acta Pharmacol Sin

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Aim: To characterize the expression and function of midkine (MK) in an in vitro embryonic stem cell (ESC) culture system. Methods: To investigate the potential roles of MK, the expression of MK in ESCs was evaluated by RT-PCR and immunocytochemistry. The effects of MK on the self-renewal of ESCs were measured using alkaline phosphatase assays, immunocytochemistry, RT-PCR and colony-forming assays. The mechanism of the growth-promoting effect of MK in mESCs was assessed by cell cycle analysis and Western blot analysis. Results: MK is expressed in mouse embryonic stem cells (mESCs), human embryonic stem cells (hESCs) and mouse embryonic fibroblasts (MEFs). MK promotes proliferation and self-renewal of mESCs both in feeder and feeder free culture systems. It also promotes self-renewal and proliferation of hESCs. Further study showed that MK promotes the growth of mESCs by inhibiting apoptosis while accelerating the progression toward the S phase, and enhances mESC self-renewal through PI3K/Akt signaling pathway. Conclusion: MK plays profound roles in ESCs. MK/PTPζ signaling pathway is a novel pathway in the signal network maintaining pluripotency of ESCs. The results extend our knowledge on pluripotency control of ESCs and the relationship between ESCs and cancers.

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Identification of midkine as a mediator for intercellular transfer of drug resistance

Cited by 71 publications

References 35 publications

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

Recruitment of insulin receptor substrate-1 and activation of NF-κB essential for midkine growth signaling through anaplastic lymphoma kinase

Promotion of self-renewal of embryonic stem cells by midkine

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