Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer

Liang, Bin; Wang, Shan; Zhu, Xue-Guang; Yu, Yizhi; Cui, Zhirong; Yu, You-zhi

doi:10.3748/wjg.v11.i5.623

Cited by 75 publications

(50 citation statements)

References 26 publications

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“…Activation of both JNK and p38 has been reported in breast carcinoma, 12 metastatic serous ovarian carcinoma 13 and in gastric cancer 14 whereas activation of JNK and p38 alone has been reported in poorly differentiated liver tumors 15 and in prostate cancer, 16 respectively. A correlation between activated JNK and early stages of nonsmall-cell lung cancers has been described.…”

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confidence: 99%

Activation of c-jun N-terminal kinase is associated with cell proliferation and shorter relapse-free period in superficial spreading malignant melanoma

2006

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Signaling pathways regulating cell proliferation and survival have become attractive targets for anticancer strategies. In the present study, we analyzed by immunohistochemistry, a panel of benign nevi, superficial spreading and nodular primary melanomas and metastases for expression of activated p38/mitogen-activated protein kinase (p-p38) and c-jun N-terminal kinase (JNK) (p-JNK) and correlated the findings with known prognostic variables. Twenty-five and 35% of the primaries and 9 and 25% of the metastases expressed variable levels of p-p38 and p-JNK, respectively. In benign nevi, 73.5% expressed p-JNK and 7% expressed p-p38. For patients with superficial spreading melanomas, high level of cytoplasmic p-JNK was associated with thicker tumors (P ¼ 0.017) and shorter disease-free survival (P ¼ 0.003) as well as with markers of cell proliferation (cyclin A (P ¼ 0.017) and p21 (P ¼ 0.021)). In nodular melanomas, nuclear p-p38 was associated with Ki-67 (P ¼ 0.012), but neither cytoplasmic nor nuclear localized p-p38 was associated with disease outcome. Of note, in superficial spreading melanomas, a positive correlation between cytoplasmic p-JNK and cytoplasmic p-extracellular signal-regulated kinase ERK1/2 (P ¼ 0.005) and p-p38 (P ¼ 0.003) was observed. Likewise, p-p38 in cytoplasm was positively associated with cytoplasmic p-ERK1/2 (Po0.0005) and p-Akt (P ¼ 0.047). In contrast, except for a positive correlation between nuclear p-p38 and membranous p-TrkA (P ¼ 0.02), no correlation between the activation status of the different signaling pathways was observed in nodular melanomas. In conclusion, our results suggest that in benign nevi activated JNK may have a role in restricting uncontrolled cell proliferation or survival. However, during tumor progression, activation of JNK is associated with cell proliferation and shorter relapse-free period for patients with superficial spreading melanomas, suggesting that the JNK activation status could be a marker for clinical outcome in at least a subgroup of malignant melanoma. In contrast, activation of p38 seems to play a less important role in development and progression of malignant melanomas.

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confidence: 99%

Activation of c-jun N-terminal kinase is associated with cell proliferation and shorter relapse-free period in superficial spreading malignant melanoma

2006

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“…Mitogen-activated protein/ERK kinase 1 (MEK1), when engineered to be constitutively active, can transform mammalian cells to a cancerous phenotype (Cowley et al 1994, Mansour et al 1994, Webb et al 1998, whereas inhibition of MAPK activity can inhibit the growth of Ras-transformed cells in vitro (Dudley et al 1995, Sebolt-Leopold et al 1999. In addition, the activated MAPK or increased levels of MAPK expression have been detected in a variety of human tumors (Oka et al 1995, Sivaraman et al 1997, Hoshino et al 1999, Kim et al 1999, Ahmed et al 2002, Satyamoorthy et al 2003, Liang et al 2005, Takata et al 2005. Thus, the MAPK signaling pathway is a potential target in cancer therapy (Duesbery et al 1999, Tecle et al 1999, Fang & Richardson 2005, Staehler et al 2005.…”

Section: Introductionmentioning

confidence: 99%

Calcitonin targets extracellular signal-regulated kinase signaling pathway in human cancers

Nakamura

Han

Nishishita

et al. 2007

Journal of Molecular Endocrinology

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The mitogen-activated protein kinases (MAPKs) signaling pathway is a potential target in cancer therapy. Constitutive phosphorylated extracellular signal-regulated kinase (ERK1/2), which is one of the MAPKs has been detected in a variety of tumors. Calcitonin (CT) is a polypeptide hormone secreted by the thyroid gland and has been used to treat the osteoporosis and humoral hypercalcemia of malignancy. We report that CT decreases ERK1/2 phosphorylation in cancer cells showing constitutive phosphorylated ERK1/2. In MDA-MB-231 cells, a breast cancer cell line showing constitutive phosphorylated ERK1/2, CT phosphorylated c-Raf at Ser 259 via the protein kinase A pathway, resulting in suppression of ERK1/2 phosphorylation. CT significantly reduced the tumor volume of MDA-MB-231 cells showing constitutive phosphorylated ERK1/2 compared with saline buffer. However, CT did not exert any significant effects on the proliferation of MCF-7 cells, a breast cancer cell line, showing non-constitutive phosphorylated ERK1/2. These novel findings indicate that CT may be used to target ERK in the treatment of cancer.

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“…Generally, the ERK signaling pathway is typically associated with cell survival, proliferation and differentiation and protecting cells against apoptosis, whereas the JNK and p38 cascades are usually involved in promoting cell growth and apoptosis (4). It has been shown that abnormal MAPK expression is correlated with tumorigenesis and metastatic potential for gastric cancer (5). Thus, identifying new tumor suppressor genes or oncogenes that participate in the MAPK pathway could lead to the discovery of new therapies for gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

Underexpressed CNDP2 Participates in Gastric Cancer Growth Inhibition through Activating the MAPK Signaling Pathway

Zhang

Miao

Xin

et al. 2013

Mol Med

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Increasing evidence suggests that cytosolic non-specific dipeptidase 2 (CNDP2) appears to do more than just perform an enzymatic activity; it is functionally important in cancers as well. Here, we show that the expression of CNDP2 is commonly downregulated in gastric cancer tissues. The ectopic expression of CNDP2 resulted in significant inhibition of cell proliferation, induction of cell apoptosis and cell cycle arrest, and suppressed gastric tumor growth in nude mice. We further revealed that the reintroduction of CNDP2 transcriptionally upregulated p38 and activated c-Jun NH 2 -terminal kinase (JNK), whereas the loss of CNDP2 increased the phosphorylation of extracellular signal-related kinase (ERK). These results suggest that CNDP2 acts as a functional tumor suppressor in gastric cancer via activation of the mitogen-activated protein kinase (MAPK) pathway.

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Increased expression of mitogen-activated protein kinase and its upstream regulating signal in human gastric cancer

Cited by 75 publications

References 26 publications

Activation of c-jun N-terminal kinase is associated with cell proliferation and shorter relapse-free period in superficial spreading malignant melanoma

Activation of c-jun N-terminal kinase is associated with cell proliferation and shorter relapse-free period in superficial spreading malignant melanoma

Calcitonin targets extracellular signal-regulated kinase signaling pathway in human cancers

Underexpressed CNDP2 Participates in Gastric Cancer Growth Inhibition through Activating the MAPK Signaling Pathway

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