SHP-1 is a target of regorafenib in colorectal cancer

Fan, Li Ching; Teng, Hao Wei; Shiau, Chung Wai; Lin, Hang; Hung, Ming-Hui; Chen, Yen‐Lin; Huang, Jui Wen; Tai, Wei-Tien; Yu, Hui; Chen, Kuen Feng

doi:10.18632/oncotarget.2191

Cited by 54 publications

(58 citation statements)

References 25 publications

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“…Therefore, on the basis of the findings detailed in the present study, the present authors hypothesize that SHP-1 contributes to EGCG-induced apoptosis by modifying the phosphorylation patterns of key apoptosis regulators, including p38α MAPK. Although a number of agonists and inhibitors of SHP-1 have been employed to treat solid tumors, these treatments are rarely used for leukemia (11,12). The finding that SHP-1 affects apoptosis in NB4 cells suggests that agonists and inhibitors of SHP-1, either alone or combination with EGCG, may also be used to treat leukemia in the future.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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 ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…However, the clinical value of cancer treatment by targeting SHP-1 is still under investigation. According to a few reports [50][51][52], several agents that regulate SHP-1 activity have been identified, and some have found efficacy against different cancer cells. In our previous work, we disclosed that regorafenib, a multiple protein kinase inhibitor, exerts anti-tumor effects by enhancing SHP-1 activity [50].…”

Section: Discussionmentioning

confidence: 99%

“…According to a few reports [50][51][52], several agents that regulate SHP-1 activity have been identified, and some have found efficacy against different cancer cells. In our previous work, we disclosed that regorafenib, a multiple protein kinase inhibitor, exerts anti-tumor effects by enhancing SHP-1 activity [50]. Dovitinib, another multiple protein kinase inhibitor, acts as a novel radiosensitizer in HCC by upregulating SHP-1 [51].…”

Section: Discussionmentioning

confidence: 99%

Targeting SHP-1–STAT3 signaling: a promising therapeutic approach for the treatment of cholangiocarcinoma

Hu¹,

Chen²,

Chen³

et al. 2017

European Journal of Cancer

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“…Deregulation of STAT3 promotes proliferation and invasiveness of human glioblastoma cells [13]. In particular, highly expressed phosphorylated (p)-STAT3 in cancer cell plays an essential role in the progression of cancer via downregulation by SHP-1 [15]. Therefore, in the current study, we tried to explore the underlying molecular mechanism of VB in glioblastoma involving SHP-1 and STAT3.…”

Section: Introductionmentioning

confidence: 99%

Verbascoside Inhibits Glioblastoma Cell Proliferation, Migration and Invasion While Promoting Apoptosis Through Upregulation of Protein Tyrosine Phosphatase SHP-1 and Inhibition of STAT3 Phosphorylation

Jia

Wang

Zou

et al. 2018

Cell Physiol Biochem

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Background/Aims: As a natural antioxidant, verbascoside (VB) is proved to be a promising method for the treatment of oxidative-stress-related neurodegenerative diseases. Thus, this study aimed to investigate the effects of VB on glioblastoma cell proliferation, apoptosis, migration, and invasion as well as the mechanism involving signal transducer and activator of transcription 3 (STAT3) and Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). Methods: U87 cells were assigned to different treatments. The MTT assay was used to test cell proliferation, flow cytometry was used to detect cell apoptosis, and a Transwell assay was used for cell migration and invasion. We analyzed the glioblastoma tumor growth in a xenograft mouse model. Western blot analysis was employed to determine the protein expression of related genes. Results: Glioblastoma cells exhibited decreased cell proliferation, migration, invasion, and increased apoptosis when treated with VB or TMZ. Western blot analysis revealed elevated SHP-1 expression and reduced phosphorylated (p)-STAT3 expression in glioblastoma cells treated with VB compared with controls. Correspondingly, in a xenograft mouse model treated with VB, glioblastoma tumor volume and growth were decreased. Glioblastoma xenograft tumors treated with VB showed elevated SHP-1, Bax, cleaved caspase-3, and cleaved PARP expression and reduced p-STAT3, Bcl-2, survivin, MMP-2, and MMP-9 expression. siRNA-SHP-1 inhibited the VB effects on glioblastoma. Conclusion: This study demonstrates that VB inhibits glioblastoma cell proliferation, migration, and invasion while promoting apoptosis via SHP-1 activation and inhibition of STAT3 phosphorylation.

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SHP-1 is a target of regorafenib in colorectal cancer

Cited by 54 publications

References 25 publications

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

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

Targeting SHP-1–STAT3 signaling: a promising therapeutic approach for the treatment of cholangiocarcinoma

Verbascoside Inhibits Glioblastoma Cell Proliferation, Migration and Invasion While Promoting Apoptosis Through Upregulation of Protein Tyrosine Phosphatase SHP-1 and Inhibition of STAT3 Phosphorylation

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