PRSS3 promotes tumour growth and metastasis of human pancreatic cancer

Jiang, Guozhong; Cao, Fang; Ren, Guoping; Gao, Dongling; Bhakta, Vipul; Zhang, Yunhan; Cao, Hua; Dong, Ziming; Zang, Weidong; Zhang, Shuijun; Wong, Hock Tsen; Hiley, Crispin; Crnogorac‐Jurčević, Tatjana; Lemoine, Nick R.; Wang, Yaohe

doi:10.1136/gut.2009.200105

Cited by 73 publications

(104 citation statements)

References 34 publications

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“…10 All primary antisera were purchased from Santa Cruz Biotechnology (Paso Robles, CA, USA). After being blocked for 1 h at 37°C in phosphate buffered saline (PBS) containing 5% goat serum and 0.3% Triton X-100, the sections were incubated with primary antibodies GFAP and vimentin, or primary antibodies p-p38MAPK and p-JNK overnight at 4°C, respectively.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Spinal sample showing p-JNK and P38 associated with the pain signaling transduction of glial cell in neuropathic pain

Cao

et al. 2014

Spinal Cord

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Objective: To investigate the signaling pathways after astrocytes were activated in neuropathic pain. Methods: Thirty-six Sprague Dawley (s.d.) rats were randomly divided into two groups (each group with 18 s.d. rats) including chronic constriction injury (CCI) of the sciatic nerve model group and sham operation group. Operation was perform ed on the right leg in all rats. The lumbar spin al cord (L4 and L5) was taken to make paraffin slices on the 1st day before operation and the 1st, 3rd, 7th, 14th and 28th day after operation in each group. Paraffin slices were labeled with p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) by immunofluorescence staining, and then were co-labeled with hexaribonucleotide binding protein-3 (NeuN), glial fibrillary acidic protein (GFAP) and anti-integrin αM (CD11b) antibody (OX-42) to explore the associations of p38MAPK and JNK with nerve cells or glial cell. Results: Compared with sham group, the pain threshold was significantly decreased, and astrocyte-activated markers, GFAP and vimentin were significantly increased in CCI group. The mean fluorescence intensities of p38MAPK and JNK were increased in the right spinal dorsal horn of CCI group. The coexpression of JNK and GFAP was found in astrocytes of the spinal dorsal horn in CCI group. Conclusion: JNK signal transduction pathway is involved in the pain signaling transduction of astrocytes.

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Section: Immunohistochemistrymentioning

confidence: 99%

Spinal sample showing p-JNK and P38 associated with the pain signaling transduction of glial cell in neuropathic pain

Cao

et al. 2014

Spinal Cord

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“…This difference may be due to the ability of cathepsin-L to degrade extracellular matrix allowing for more tumor growth in those tumors expressing high levels of cathepsin-L. Mesotrypsinogen (PRSS3) has been found to be overexpressed in pancreatic cancer cell lines and promotes cell proliferation and invasion in cell culture, while in vivo it causes both tumor growth and metastasis. This data suggests that modulation of the PRSS3 signaling pathway may be a viable approach for treating pancreatic cancer (Jiang et al, 2010).…”

Section: Role Of Premature Trypsinogen Activationmentioning

confidence: 99%

Risk Factors for Pancreatic Cancer: Underlying Mechanisms and Potential Targets

2015

Frontiers Research Topics

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Purpose of the review: Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent findings: Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer.Summary: Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

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“…These alternative isoforms, trypsinogens 4 and 5, do not possess classic signal sequences, and the mechanisms by which they are trafficked and activated are not yet fully elucidated, but functional studies provide evidence for significant roles for active mesotrypsin in keratinocyte differentiation and skin desquamation (6,7). PRSS3 transcripts, primarily encoding trypsinogen 4, are also expressed in many epithelial cells and cancers, and functional studies likewise provide evidence for extracellular roles for active mesotrypsin in tumor progression of breast (8), pancreatic (9), and prostate cancers (10,11). An unusual feature of mesotrypsin is its extreme resistance to endogenous proteinaceous trypsin inhibitors (1,12,13) and its ability to digest some of these inhibitors as substrates (6,14,15).…”

Section: Mesotrypsin Is An Isoform Of Trypsin That Is Uniquely Resistmentioning

confidence: 99%

Sequence and Conformational Specificity in Substrate Recognition

Pendlebury

Wang

Henin

et al. 2014

Journal of Biological Chemistry

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Background: Mesotrypsin targets protease inhibitors as substrates; substrate recognition depends on sequence and conformational motifs. Results: Mesotrypsin cleaves three human Kunitz domains as specific substrates, but other similarly shaped substrates are cleaved less efficiently. Conclusion: Substrate conformation aids recognition by mesotrypsin but is not sufficient for efficient cleavage. Significance: Mesotrypsin cleavage of human Kunitz domains may contribute to cancer progression.

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PRSS3 promotes tumour growth and metastasis of human pancreatic cancer

Abstract: PRSS3 plays an important role in the progression, metastasis and prognosis of human pancreatic cancer. Targeting the PRSS3 signalling pathway may be an effective and feasible approach for treatment of this lethal cancer.

Cited by 73 publications

References 34 publications

Spinal sample showing p-JNK and P38 associated with the pain signaling transduction of glial cell in neuropathic pain

Spinal sample showing p-JNK and P38 associated with the pain signaling transduction of glial cell in neuropathic pain

Risk Factors for Pancreatic Cancer: Underlying Mechanisms and Potential Targets

Sequence and Conformational Specificity in Substrate Recognition

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