Transcriptional regulation of survivin by c‐Myc in BCR/ABL‐transformed cells: implications in anti‐leukaemic strategy

Fang, Zhi; Dong, Chunlan; Chen, Zhong; Zhou, Bin; Liu, Na; Lan, Hai; Liang, Lu; Liao, Wen Bin; Zhang, Lei; Han, Zhong Chao

doi:10.1111/j.1582-4934.2008.00549.x

Cited by 33 publications

(27 citation statements)

References 54 publications

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“…Prior evidence had established that JAK2 inhibition reduced survivin levels in AML cells (20). Furthermore, Fang and colleagues proposed that survivin upregulation was largely controlled at the transcriptional level through a JAK2-dependent mechanism (17). Our findings suggested a role for JAK2 in modulating survivin levels in CML cells.…”

Section: Survivin Induction By Bcr-abl Tyrosine Kinase Activity Involsupporting

confidence: 56%

“…Our findings suggested that BCR-ABL might directly regulate survivin expression in CML cells and indeed, subsequent manuscripts have shown that BCR-ABL upregulates survivin at both the transcriptional and protein levels (15)(16)(17). However, these reports used single immortalized cell lines and attributed BCR-ABL-dependent induction of survivin to different signaling pathways.…”

Section: Survivin Induction By Bcr-abl Tyrosine Kinase Activity Involmentioning

confidence: 59%

“…Carter and colleagues had previously suggested that the RAS/ RAF/MAPK cascade was involved in BCR-ABL-dependent upregulation of survivin (16). In a different cell line, Fang and colleagues identified JAK2/PI3K/c-myc signaling as the main regulator of BCR-ABL-dependent induction of survivin (17). However, when we suppressed mitogen-activated protein kinase (MAPK) activity with PD98059 in a set of 4 human CML cells, we detected a reduction in survivin levels only in the K562 line (Fig.…”

Section: Survivin Induction By Bcr-abl Tyrosine Kinase Activity Involmentioning

confidence: 99%

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Suppression of Survivin Induced by a BCR-ABL/JAK2/STAT3 Pathway Sensitizes Imatinib-Resistant CML Cells to Different Cytotoxic Drugs

Stella

Tirrò

Conte

et al. 2013

Molecular Cancer Therapeutics

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The BCR-ABL oncoprotein of chronic myelogenous leukemia (CML) displays exclusive cytoplasmic localization and constitutive tyrosine kinase activity leading to the activation of different pathways that favor cell proliferation and survival. BCR-ABL induces survivin expression at both the mRNA and protein level, thus inhibiting the apoptotic machinery of CML cells and contributing to the expansion of the leukemic clone. We report that, in human CML cell lines, BCR-ABL-mediated upregulation of survivin involves the JAK2/STAT3 pathway since silencing of either protein caused a consistent reduction in survivin expression. Cell lines unresponsive to imatinib mesylate (IM) because of BCR-ABL gene amplification were not resensitized to the drug after survivin downregulation. However, cells insensitive to IM because of point mutations in the BCR-ABL kinase domain were highly responsive to hydroxyurea (HU) after survivin silencing. To address the possible clinical applications of our results, we used shepherdin, a cell-permeable peptidomimetic compound that downregulates survivin expression by preventing its interaction with Hsp90. Incubation with shepherdin of immortalized cell lines both sensitive and resistant to IM enhanced cell death induced by HU and doxorubicin. Similarly, the combination of shepherdin with first-and second-generation tyrosine kinase inhibitors reduced the colony-forming potential of human progenitors derived from both patients with IMsensitive and IM-resistant CML. These results suggest that strategies aimed at reducing survivin levels may represent a potential therapeutic option for patients with CML unresponsive to IM.

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Section: Survivin Induction By Bcr-abl Tyrosine Kinase Activity Involsupporting

confidence: 56%

Section: Survivin Induction By Bcr-abl Tyrosine Kinase Activity Involmentioning

confidence: 59%

Section: Survivin Induction By Bcr-abl Tyrosine Kinase Activity Involmentioning

confidence: 99%

See 1 more Smart Citation

Suppression of Survivin Induced by a BCR-ABL/JAK2/STAT3 Pathway Sensitizes Imatinib-Resistant CML Cells to Different Cytotoxic Drugs

Stella

Tirrò

Conte

et al. 2013

Molecular Cancer Therapeutics

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“…In nonmalignant proliferating cells, the expression of survivin is regulated in a cell cycle-dependent manner (6,7). The upregulation of survivin expression in tumors does not seem to be dependent solely on the cell cycle, however, given that it occurs in tumor cells that are not actively cycling (4,8,9). Indeed, growth factors have been found to regulate survivin expression in endothelial cells and neuroblastoma cells (10,11).…”

Section: Introductionmentioning

confidence: 99%

Role of Survivin in EGFR Inhibitor–Induced Apoptosis in Non–Small Cell Lung Cancers Positive for EGFR Mutations

Okamoto

et al. 2010

Cancer Research

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The molecular mechanism by which epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) induce apoptosis in non-small cell-lung cancer (NSCLC) cells that are positive for activating mutations of the EGFR remains unclear. In this study, we report the effects of the EGFR-TKI gefitinib on expression of the antiapoptotic protein survivin that have functional consequences in EGFR mutation-positive NSCLC cells. Immunoblot analysis revealed that gefitinib downregulated survivin expression, likely through inhibition of the PI3K-AKT signaling pathway, in NSCLC cells positive for EGFR mutation. Stable overexpression of survivin attenuated gefitinib-induced apoptosis and also inhibited the antitumor effect of gefitinib in human tumor xenografts. Furthermore, the combination of survivin overexpression with inhibition of the gefitinib-induced upregulation of the proapoptotic protein BIM attenuated gefitinib-induced apoptosis to a greater extent than either approach alone. Our results indicate that downregulation of survivin plays a pivotal role in gefitinibinduced apoptosis in EGFR mutation-positive NSCLC cells. Furthermore, they suggest that simultaneous interruption of the PI3K-AKT-survivin and MEK-ERK-BIM signaling pathways is responsible for EGFR-TKIinduced apoptotic death in these cells.

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“…For example, several groups have found that BCR-ABL promotes uncontrolled proliferation through AKT-mediated inactivation of cell cycle inhibitors such as p21 and p27, possibly through upregulation of the E3 ubiquitin ligase, SKP2 [229][230][231]. Reported mechanisms for PI3K-mediated enhanced survival in the presence of BCR-ABL include downregulation of the HOXA10 gene and c-Myc-mediated upregulation of the anti-apoptosis protein survivin [232,233].…”

Section: Chronic Myeloid Leukemia (Cml)mentioning

confidence: 97%

Phospho-Inositol-3-Kinase Activity and Dysregulation in Pediatric Leukemia and Lymphoma

Goodwin

Chan

2016

Cancer Drug Discovery and Development

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Transcriptional regulation of survivin by c‐Myc in BCR/ABL‐transformed cells: implications in anti‐leukaemic strategy

Abstract: BCR/ABL can cause chronic myelogenous leukaemia (CML) in part by altering the transcription of specific genes with growth-and

Cited by 33 publications

References 54 publications

Suppression of Survivin Induced by a BCR-ABL/JAK2/STAT3 Pathway Sensitizes Imatinib-Resistant CML Cells to Different Cytotoxic Drugs

Suppression of Survivin Induced by a BCR-ABL/JAK2/STAT3 Pathway Sensitizes Imatinib-Resistant CML Cells to Different Cytotoxic Drugs

Role of Survivin in EGFR Inhibitor–Induced Apoptosis in Non–Small Cell Lung Cancers Positive for EGFR Mutations

Phospho-Inositol-3-Kinase Activity and Dysregulation in Pediatric Leukemia and Lymphoma

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