Sprouty 2: a novel attenuator of B-cell receptor and MAPK-Erk signaling in CLL

Shukla, Ashima; Rai, Karan; Shukla, Vipul; Chaturvedi, Nagendra K.; Bociek, R. Gregory; Pirruccello, Samuel J.; Band, Hamid; Lu, Runqing; Joshi, Shantaram S.

doi:10.1182/blood-2015-09-669317

Cited by 23 publications

(20 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we found SPRY2 regulated the expression of c-RAF, p-MEK, and p-ERK in HCC, but had no effect on k-RAS, MEK and ERK. Therefore, SPRY2 might exert its ERK inhibitor role via suppressing c-RAF in HCC, which were consistent with prior studies in leukemia 38 , 39 . RAF-MAPK/ERK was an important signaling for targeting drugs such as regorafenib and sorafenib, thus our findings potentially provided a new clue for developing anovel therapeutic approach for HCC 40 .…”

Section: Discussionsupporting

confidence: 91%

miR-330-5p targets SPRY2 to promote hepatocellular carcinoma progression via MAPK/ERK signaling

Xiao

Yang

et al. 2018

Oncogenesis

View full text Add to dashboard Cite

MicroRNAs (miRNAs) have been identified as critical modulators of cell proliferation and growth, which are the major causes of cancer progression including hepatocellular carcinoma (HCC). Our previous miRNA microarray data have shown that miR-330-5p was always upregulated in HCC. However, the accurate role of miR-330-5p in HCC is still uncertain. Here, we report that miR-330-5p expression is upregulated in HCC tissues and cell lines, and is associated with tumor size, tumor nodule number, capsule formation and Tumor Node Metastasis (TNM) stage in HCC patients. Overexpression of miR-330-5p promotes proliferation and growth of HCC cells in vitro and in vivo, while miR-330-5p knockdown has the inverse effect. Moreover, using miRNA databases and dual luciferase report assay, we find miR-330-5p directly binds to the 3′-untranslated region (3′-UTR) of Sprouty2 (SPRY2). Then we find the novel biofunctional role of SPRY2 inactivation in promoting HCC progression. Finally, we confirm that miR-330-5p suppresses SPRY2 to promote proliferation via mitogen-activated protein kinases (MAPK)/extracellular regulated kinase (ERK) signaling in HCC. Taken together, our findings demonstrate the critical role of miR-330-5p in promoting HCC progression via targeting SPRY2 to activate MAPK/ERK signaling, which may provide a novel and promising prognostic marker and therapeutic target for HCC.

show abstract

Section: Discussionsupporting

confidence: 91%

miR-330-5p targets SPRY2 to promote hepatocellular carcinoma progression via MAPK/ERK signaling

Xiao

Yang

et al. 2018

Oncogenesis

View full text Add to dashboard Cite

show abstract

“…An informed written consent was obtained from each participant. The cells were isolated as previously described [36]. …”

Section: Methodsmentioning

confidence: 99%

Interferon regulatory factor 4 attenuates Notch signaling to suppress the development of chronic lymphocytic leukemia

Shukla

Joshi

et al. 2016

Oncotarget

Self Cite

View full text Add to dashboard Cite

Molecular pathogenesis of Chronic Lymphocytic Leukemia (CLL) is not fully elucidated. Genome wide association studies have linked Interferon Regulatory Factor 4 (IRF4) to the development of CLL. We recently established a causal relationship between low levels of IRF4 and development of CLL. However, the molecular mechanism through which IRF4 suppresses CLL development remains unclear. Deregulation of Notch signaling pathway has been identified as one of the most recurrent molecular anomalies in the pathogenesis of CLL. Yet, the role of Notch signaling as well as its regulation during CLL development remains poorly understood. Previously, we demonstrated that IRF4 deficient mice expressing immunoglobulin heavy chain Vh11 (IRF4−/−Vh11) developed spontaneous CLL with complete penetrance. In this study, we show that elevated Notch2 expression and the resulting hyperactivation of Notch signaling are common features of IRF4−/−Vh11 CLL cells. Our studies further reveal that Notch signaling is indispensable for CLL development in the IRF4−/−Vh11 mice. Moreover, we identify E3 ubiquitin ligase Nedd4, which targets Notch for degradation, as a direct target of IRF4 in CLL cells and their precursors. Collectively, our studies provide the first in vivo evidence for an essential role of Notch signaling in the development of CLL and establish IRF4 as a critical regulator of Notch signaling during CLL development.

show abstract

“…In B‐cell lymphoma, Sprouty2 is epigenetically silenced and promotes cell proliferation . Sprouty2 is also downregulated in chronic lymphocytic leukemia and is an important negative regulator of B‐cell receptor‐mediated ERK activation . In multiple myeloma, Sprouty2 is downregulated by miR‐21 expression .…”

Section: Roles Of Sprouty/spred During Tumorigenesis and Metastasismentioning

confidence: 99%

“…2 Sprouty2 is also downregulated in chronic lymphocytic leukemia and is an important negative regulator of B-cell receptor-mediated ERK activation. 52 In multiple myeloma, Sprouty2 is downregulated by miR-21 expression. 15,86 High expression of Sprouty4 is associated with a favorable prognosis in patients with AML.…”

Section: Sprouty/spred and Hematological Malignanciesmentioning

confidence: 99%

The Sprouty/Spred family as tumor suppressors: Coming of age

Kawazoe

Taniguchi

2019

Cancer Science

View full text Add to dashboard Cite

The Ras/Raf/ERK pathway is one of the most frequently dysregulated signaling pathways in various cancers. In some such cancers, Ras and Raf are hotspots for mutations, which cause continuous activation of this pathway. However, in some other cancers, it is known that negative regulators of the Ras/Raf/ERK pathway are responsible for uncontrolled activation. The Sprouty/Spred family is broadly recognized as important negative regulators of the Ras/Raf/ERK pathway, and its expression is downregulated in many malignancies, leading to hyperactivation of the Ras/Raf/ERK pathway. After the discovery of this family, intensive research investigated the mechanism by which it suppresses the Ras/Raf/ERK pathway and its roles in developmental and pathophysiological processes. In this review, we discuss the complicated roles of the Sprouty/Spred family in tumor initiation, promotion, and progression and its future therapeutic potential.

show abstract

Sprouty 2: a novel attenuator of B-cell receptor and MAPK-Erk signaling in CLL

Cited by 23 publications

References 45 publications

miR-330-5p targets SPRY2 to promote hepatocellular carcinoma progression via MAPK/ERK signaling

miR-330-5p targets SPRY2 to promote hepatocellular carcinoma progression via MAPK/ERK signaling

Interferon regulatory factor 4 attenuates Notch signaling to suppress the development of chronic lymphocytic leukemia

The Sprouty/Spred family as tumor suppressors: Coming of age

Contact Info

Product

Resources

About