The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

Zhang, Rong; Yang, Wenyan; Li, Ying Chun; Zhang, Guo Jun; Yao, Kun; Hu, Rong; Wu, Bin

doi:10.1159/000369685

Cited by 15 publications

(11 citation statements)

References 32 publications

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“…OPN was detected with considerable polymorphism, recent study found that the -443C>T polymorphism of OPN was able to serve for susceptibility as well as chemotherapy response of AML [29]. OPN is thought to contain bioactive regions on its surface, along with its RGD sequences, that can exhibit multiple biological functions, including the activation of some regulatory and structural proteins when connecting with its integrin receptors [30, 31].…”

Section: Discussionmentioning

confidence: 99%

Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

Huang

Quan

Chen

et al. 2017

Cell Physiol Biochem

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Background: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. Methods: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. Results: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. Conclusion: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.

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Section: Discussionmentioning

confidence: 99%

Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

Huang

Quan

Chen

et al. 2017

Cell Physiol Biochem

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“…One of the most studied OPN single-nucleotide polymorphism is rs11730582, whose −443 CC genotype has been associated with higher expression of OPN and increased cancer risk in acute myeloid leukemia, glioma, and papillary thyroid cancer. Interestingly, in other tumors such as hepatocellular carcinoma (HCC), breast cancer, nasopharyngeal carcinoma, and melanoma, the −443 TT genotype, rather than the C allele, correlates with increased expression of OPN [50–56]. In this regard, it has been proposed that the proto-oncogene c-Myb mediates induction of OPN expression levels from the C allele in some tumors, whereas in other malignancies, a yet unidentified transcription factor could activate transcription of OPN from the T allele [56].…”

Section: Opn General Featuresmentioning

confidence: 99%

Osteopontin at the Crossroads of Inflammation and Tumor Progression

Castello

Raineri

Salmi

et al. 2017

Mediators of Inflammation

149

132

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Complex interactions between tumor and host cells regulate systemic tumor dissemination, a process that begins early at the primary tumor site and goes on until tumor cells detach themselves from the tumor mass and start migrating into the blood or lymphatic vessels. Metastatic cells colonize the target organs and are capable of surviving and growing at distant sites. In this context, osteopontin (OPN) appears to be a key determinant of the crosstalk between cancer cells and the host microenvironment, which in turn modulates immune evasion. OPN is overexpressed in several human carcinomas and has been implicated in inflammation, tumor progression, and metastasis. Thus, it represents one of the most attracting targets for cancer therapy. Within the tumor mass, OPN is secreted in various forms either by the tumor itself or by stroma cells, and it can exert either pro- or antitumorigenic effects according to the cell type and tumor microenvironment. Thus, targeting OPN for therapeutic purposes needs to take into account the heterogeneous functions of the multiple OPN forms with regard to cancer formation and progression. In this review, we will describe the role of systemic, tumor-derived, and stroma-derived OPN, highlighting its pivotal role at the crossroads of inflammation and tumor progression.

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“…In spite of recent improvement in therapeutic strategies, AML remains an incurable disease for majority of patients [30,32,33]. Predominantly, development of chemoresistance is a major bottleneck limiting the therapeutic efficacy in AML therapy [34].…”

Section: Discussionmentioning

confidence: 99%

Anti-Leukemic Activity of Shikonin: Role of ERP57 in Shikonin Induced Apoptosis in Acute Myeloid Leukemia

Trivedi

Müller

Rathore

et al. 2016

Cell Physiol Biochem

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Background/Aims: ER-Stress and activation of unfolded protein response belong to the major factors involved in chemoresistance in cancer cells. In this study we investigated the effect of shikonin on the survival of acute myeloid leukemia cells and the role of ER-stress protein ERP57, a protein disulfide isomerase, in improvement of chemotherapy. Methods: Using MTT assay we studied cytotoxic effects of shikonin on HL-60 cells. The flow cytometry was adopted to examine the shikonin induced mode of cell death in HL-60 cells. The overall protein expression alteration resulting from shikonin treatment was investigated using proteomics methods. Western blotting was performed to quantify the alteration in protein expression in HL-60 after shikonin treatment. Silencing and overexpression studies were carried out to highlight the therapeutic role of ERP57 in shikonin effect on AML cells. Results: Shikonin induces apoptosis in HL-60 cells without significant effect on Primary cells from healthy volunteers. The apoptotic effect was dose and time dependent and was accompanied by strong alteration in cell proteome. Among the proteins targeted by shikonin, ERP57 was significantly downregulated in HL-60 after treatment. Compared to healthy control ERP57 was found to be highly expressed in AML cell line HL60 and was downregulated after shikonin treatment. Overexpression of ERP57 protected HL-60 from shikonin induced apoptosis, whereas knockdown of ERP57 expression resulted in increase in shikonin induced apoptosis. Conclusions: Our results demonstrate that ERP57 plays a crucial role in resistance towards shikonin induced apoptosis in AML cells. Targeting of ERP57 might offer a new therapeutic option for the treatment of acute myeloid leukemia.

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The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

Cited by 15 publications

References 32 publications

Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

Osteopontin at the Crossroads of Inflammation and Tumor Progression

Anti-Leukemic Activity of Shikonin: Role of ERP57 in Shikonin Induced Apoptosis in Acute Myeloid Leukemia

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