SUMOylation of insulin-like growth factor 1 receptor, promotes proliferation in acute myeloid leukemia

Zhang, Jian; Huang, Fangfang; Wu, Daichao; Li, Wenjin; Zhan, Huien; Peng, Minyuan; Peng, Fang; Cao, Pengfei; Zhang, Mengmeng; Zeng, Hui; Chen, Fangping

doi:10.1016/j.canlet.2014.11.052

Cited by 21 publications

(20 citation statements)

References 21 publications

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“…These data provide direct evidence that SUMOylation is important for IGF‐1R‐induced cell proliferation. In consistence with our finding, Zhang et al (2015) showed that co‐expression of IGF‐1R containing SUMOylation site mutations (i.e., K1025R and K1100R) substantially decreased proliferation in acute myeloid leukemia cells. Furthermore, a correlation between estrogen receptor positive breast cancer cells and SUMOylated IGF‐1R in cell nuclei was demonstrated by Sarfstein et al (2012).…”

Section: Discussionsupporting

confidence: 92%

“…The finding that co‐expression of IGF‐1R K1025R/ K1100R in leukemia cells decreased proliferation but did not cause apoptosis (Zhang et al, 2015) supports this hypothesis. Under the experimental conditions (basal) applied in the present study, we could not detect any difference in rate of apoptotic cell death in R‐WT and R‐TSM.…”

Section: Discussionmentioning

confidence: 88%

“…Hypothetically, the canonical IGF-1R signaling may affect cell growth predominantly through increasing cell survival (e.g., Baserga, 2009;Resnicoff et al, 1996), whereas SUMO-dependent signaling mainly affects cell proliferation. The finding that co-expression of IGF-1R K1025R/ K1100R in leukemia cells decreased proliferation but did not cause apoptosis (Zhang et al, 2015) The mechanism underlying the ability of SUMOylated IGF-1R to induce proliferation and cell cycle progression remain requires further studies. In the current study, we found increased expression of cyclin D1, cyclin A, and CDK2 as well as decrease in p27 in R-WT cells, events that are known to drive cells from G1-to and through the S-phase.…”

Section: Discussionmentioning

confidence: 99%

“…It has been proposed as a marker of overall survival and progression-free survival in patients with soft tissue sarcomas and osteosarcomas treated with anti-IGF-1R antibody therapy (Asmane et al, 2012). High levels of nIGF-1R has also been reported in several cancer cell lines, including human alveolar rhabdomyosarcoma, hepatocellular, prostate, and breast carcinoma, as well as acute myeloid leukemia cells (Aslam et al, 2013;Chein, Kuo, Liao, Wang, & Yu, 2016;Deng et al, 2011;Sarfstein et al, 2012;Zhang et al, 2015).…”

mentioning

confidence: 99%

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SUMO‐modified insulin‐like growth factor 1 receptor (IGF‐1R) increases cell cycle progression and cell proliferation

Lin

Liu

Waraky

et al. 2017

Journal Cellular Physiology

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Increasing number of studies have shown nuclear localization of the insulin‐like growth factor 1 receptor (nIGF‐1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF‐1R have, however, still not been disclosed. Previously, we reported that IGF‐1R translocates to cell nucleus and modulates gene expression by binding to enhancers, provided that the receptor is SUMOylated. In this study, we constructed stable transfectants of wild type IGF1R (WT) and triple‐SUMO‐site‐mutated IGF1R (TSM) using igf1r knockout mouse fibroblasts (R‐). Cell clones (R‐WT and R‐TSM) expressing equal amounts of IGF‐1R were selected for experiments. Phosphorylation of IGF‐1R, Akt, and Erk upon IGF‐1 stimulation was equal in R‐WT and R‐TSM. WT was confirmed to enter nuclei. TSM did also undergo nuclear translocation, although to a lesser extent. This may be explained by that TSM heterodimerizes with insulin receptor, which is known to translocate to cell nuclei. R‐WT proliferated substantially faster than R‐TSM, which did not differ significantly from the empty vector control. Upon IGF‐1 stimulation G1‐S‐phase progression of R‐WT increased from 12 to 38%, compared to 13 to 20% of R‐TSM. The G1‐S progression of R‐WT correlated with increased expression of cyclin D1, A, and CDK2, as well as downregulation of p27. This suggests that SUMO‐IGF‐1R affects upstream mechanisms that control and coordinate expression of cell cycle regulators. Further studies to identify such SUMO‐IGF‐1R dependent mechanisms seem important.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

SUMO‐modified insulin‐like growth factor 1 receptor (IGF‐1R) increases cell cycle progression and cell proliferation

Lin

Liu

Waraky

et al. 2017

Journal Cellular Physiology

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“…Sox2 + epithelial stem cells exist transiently during the molar development, and sonic hedgehog-glioma-associated oncogene 1 (Shh-Gli1) activity provides a niche for maintenance of these stem cells. However, loss of Smad4 results in ectopic SHH-Gli1 signaling and maintenance of Sox2 + cells [ 9 ]. This study has proved the importance of crosstalk between BMP and SHH signaling pathways in the regulation of epithelial stem cell fate during odontogenesis.…”

Section: Shh Signaling Pathwaymentioning

confidence: 94%

Signaling Pathways in Dental Stem Cells During Their Maintenance and Differentiation

Liu

Zhou

et al. 2016

Stem Cell Biology and Regenerative Medicine

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The important roles of protein SUMOylation in the occurrence and development of leukemia and clinical implications

Zhao

Zhang

Chen

et al. 2020

Journal Cellular Physiology

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Leukemia is a severe malignancy of the hematopoietic system, which is characterized by uncontrolled proliferation and dedifferentiation of immature hematopoietic precursor cells in the lymphatic system and bone marrow. Leukemia is caused by alterations of the genetic and epigenetic regulation of processes underlying hematologic malignancies, including SUMO modification (SUMOylation). Small ubiquitin‐like modifier (SUMO) proteins covalently or noncovalently conjugate and modify a large number of target proteins via lysine residues. SUMOylation is a small ubiquitin‐like modification that is catalyzed by the SUMO‐specific activating enzyme E1, the binding enzyme E2, and the ligating enzyme E3. SUMO is covalently linked to substrate proteins to regulate the cellular localization of target proteins and the interaction of target proteins with other biological macromolecules. SUMOylation has emerged as a critical regulatory mechanism for subcellular localization, protein stability, protein–protein interactions, and biological function and thus regulates normal life activities. If the SUMOylation process of proteins is affected, it will cause a cellular reaction and ultimately lead to various diseases, including leukemia. There is growing evidence showing that a large number of proteins are SUMOylated and that SUMOylated proteins play an important role in the occurrence and development of various types of leukemia. Targeting the SUMOylation of proteins alone or in combination with current treatments might provide powerful targeted therapeutic strategies for the clinical treatment of leukemia.

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SUMOylation of insulin-like growth factor 1 receptor, promotes proliferation in acute myeloid leukemia

Cited by 21 publications

References 21 publications

SUMO‐modified insulin‐like growth factor 1 receptor (IGF‐1R) increases cell cycle progression and cell proliferation

SUMO‐modified insulin‐like growth factor 1 receptor (IGF‐1R) increases cell cycle progression and cell proliferation

Signaling Pathways in Dental Stem Cells During Their Maintenance and Differentiation

The important roles of protein SUMOylation in the occurrence and development of leukemia and clinical implications

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