SHP-1 Plays a Crucial Role in CD40 Signaling Reciprocity

Khan, Tabish; Srivastava, Neetu; Srivastava, Ankita; Sareen, Archana; Mathur, Ramkumar; Chande, Ajit; Krishnasastry, M.V.; Roy, Somenath; Mukhopadhyaya, Robin; Saha, Bhaskar

doi:10.4049/jimmunol.1400620

Cited by 36 publications

(24 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SHP-1 inhibits the activation of STAT3, NF-kB, and AKT signaling pathways in HCC SHP-1 modulates the cellular signals that involve in PI3K/AKT, JAK/STAT, MAPKs, and NF-kB (33)(34)(35)(36). The activities of these signaling pathways are closely associated with the hepatocarcinogenesis and progression of HCC (37)(38)(39)(40)(41).…”

Section: Shp-1 Acts As a Tumor Suppressor Of Hcc In Micementioning

confidence: 99%

SHP-1 Acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression

et al. 2018

View full text Add to dashboard Cite

Src homology region 2 (SH2) domain-containing phosphatase 1 (SHP-1, also known as PTPN6) is a nonreceptor protein tyrosine phosphatase that acts as a negative regulator of inflammation. Emerging evidence indicates that SHP-1 plays a role in inhibiting the progression of hepatocellular carcinoma (HCC). However, the role of SHP-1 in hepatocarcinogenesis remains unknown. Here, we find that levels of SHP-1 are significantly downregulated in human HCC tissues compared with those in noncancerous tissues ( < 0.001) and inversely correlate with tumor diameters ( = -0.4130, = 0.0002) and serum α-fetoprotein levels ( = 0.047). Reduced SHP-1 expression was associated with shorter overall survival of patients with HCC with HBV infection. Overexpression of SHP-1 suppressed proliferation, migration, invasion, and tumorigenicity of HCC cells, whereas knockdown of SHP-1 enhanced the malignant phenotype. Moreover, knockout of in hepatocytes ( ) enhanced hepatocarcinogenesis induced by diethylnitrosamine (DEN) as well as metastasis of primary liver cancer in mice. Furthermore, systemic delivery of SHP-1 by an adenovirus expression vector exerted a therapeutic effect in an orthotopic model of HCC in NOD/SCID mice and DEN-induced primary liver cancers in mice. In addition, SHP-1 inhibited the activation of JAK/STAT, NF-κB, and AKT signaling pathways, but not the MAPK pathway in primary hepatocytes from DEN-treated mice and human HCC cells. Together, our data implicate SHP-1 as a tumor suppressor of hepatocarcinogenesis and HCC progression and propose it as a novel prognostic biomarker and therapeutic target of HCC. The nonreceptor protein tyrosine phosphatase SHP-1 acts as a tumor suppressor in hepatocellular carcinoma. .

show abstract

Section: Shp-1 Acts As a Tumor Suppressor Of Hcc In Micementioning

confidence: 99%

SHP-1 Acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Taken together, these events favored a parasite burden and confirmed that the CD40/MAPK pathway was important for L. major subversion of the host’s immune response. However, the specific mechanism surrounding augmented IL-10 production remained unknown until Srivastava et al (2011) and Khan et al (2014) noted the participation of phosphatases in this process. Srivastava et al (2011) demonstrated that in L. major infection, the phosphatases, MKP-1 and MKP-3, were differentially expressed.…”

Section: Leishmania Spp Subvert the Mapk Pathway By Activatmentioning

confidence: 99%

The Mitogen-Activated Protein Kinase (MAPK) Pathway: Role in Immune Evasion by Trypanosomatids

et al. 2016

View full text Add to dashboard Cite

Leishmania spp. and Trypanosoma cruzi are the causative agents of leishmaniasis and Chagas disease, respectively, two neglected tropical diseases that affect about 25 million people worldwide. These parasites belong to the family Trypanosomatidae, and are both obligate intracellular parasites that manipulate host signaling pathways and the innate immune system to establish infection. Mitogen-activated protein kinases (MAPKs) are serine and threonine protein kinases that are highly conserved in eukaryotes, and are involved in signal transduction pathways that modulate physiological and pathophysiological cell responses. This mini-review highlights existing knowledge concerning the mechanisms that Leishmania spp. and T. cruzi have evolved to target the host’s MAPK signaling pathways and highjack the immune response, and, in this manner, promote parasite maintenance in the host.

show abstract

“…A number of studies indicated that p38α MAPK is a downstream target of SHP-1 (31,32). However, whether the p38α MAPK signaling pathway contributes to EGCG-induced NB4 cell apoptosis has not been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin‑3‑gallate induces apoptosis in acute promyelocytic leukemia cells via a SHP‑1‑p38α MAPK‑Bax cascade

et al. 2017

View full text Add to dashboard Cite

Abstract. Acute promyelocytic leukemia (APL) is characterized by a specific chromosomal translation, resulting in a fusion gene that affects the differentiation, proliferation and apoptosis of APL cells. Epigallocatechin-3-gallate (EGCG), a catechin, exhibits numerous biological functions, including antitumor activities. Previous studies have reported that EGCG induces apoptosis in NB4 cells. However, the molecular mechanism underlying EGCG-induced apoptosis remains unclear. The present study aimed to determine the molecular basis of EGCG-induced apoptosis in NB4 cells. EGCG treatment significantly inhibited the viability of NB4 cells in a dose-dependent manner. In addition, EGCG treatment induced apoptosis and increased the levels of (Bcl-2-like protein 4) Bax protein expression. Moreover, EGCG treatment was able to increase phosphorylated (p)-p38α mitogen-activated protein kinase (MAPK) and Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1) expression. Pretreatment with PD169316 (a p38 MAPK inhibitor) partially blocked EGCG-induced apoptosis and inhibited EGCG-mediated Bax expression. Similarly, pretreatment with NSC87877, an inhibitor of SHP-1, partially blocked EGCG-induced apoptosis and inhibited EGCG-mediated increases in p-p38α MAPK and Bax expression. Therefore, the results of the present study indicate that EGCG is able to induce apoptosis in NB4 cells via the SHP-1-p38αMAPK-Bax cascade. IntroductionAcute promyelocytic leukemia (APL), a unique subtype of acute myeloid leukemia, is characterized by a translocation between chromosomes 15 and 17 that encodes the oncogenic fusion protein promyelocytic leukemia/retinoic acid receptor-α (PML/RARα) (1). PML-RARα has an essential role in the development of APL by interfering with target genes that control differentiation, proliferation and apoptosis of APL cells (2). Considerable success in treating APL has been achieved using all-trans retinoic acid (3) and arsenic trioxide (4) in clinical settings. However, the toxicity of these molecules and the prevalence of drug-resistant forms of APL limit the clinical application of these drugs (5). Therefore, novel therapeutics to treat APL are urgently required.Src homology 1 domain-containing protein tyrosine phosphatase (SHP-1), also known as PTPN6 (6), consists of 17 exons and 16 introns and spans ~17 kb (7). SHP-1 controls the changes in the levels of intracellular phosphorylation, including JAK/STAT (8). SHP-1 exerts multiple biological functions through the alteration of several signaling pathways (9,10). A number of agonists and inhibitors of SHP-1 have been applied in clinical cancer therapies. For example, γ-tocotrienol (11) and regorafenib (12) have been used to treat breast tumors and colorectal cancer, respectively. Studies have reported that SHP-1 is highly expressed in normal hematopoietic cells (13) but weakly expressed in hematological malignancies, including Burkitt's lymphoma (14), APL (15) and chronic myeloid leukemia (16). Therefore, the present authors hypothesize that increases ...

show abstract

SHP-1 Plays a Crucial Role in CD40 Signaling Reciprocity

Cited by 36 publications

References 36 publications

SHP-1 Acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression

SHP-1 Acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression

The Mitogen-Activated Protein Kinase (MAPK) Pathway: Role in Immune Evasion by Trypanosomatids

Epigallocatechin‑3‑gallate induces apoptosis in acute promyelocytic leukemia cells via a SHP‑1‑p38α MAPK‑Bax cascade

Contact Info

Product

Resources

About