The Relationship between Over-expression of Glial Cell-derived Neurotrophic Factor and Its RET Receptor with Progression and Prognosis of Human Pancreatic Cancer

Zeng, Qing‐Yin; Cheng, Yuanda; Zhu, Qi; Yu, Zheng; Wu, Ximei; Huang, Kate; Zhou, Meng; Han, Sang-Hyun; Zhang, Q

doi:10.1177/147323000803600406

Cited by 69 publications

(57 citation statements)

References 20 publications

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“…Patients with a surgically resected pancreatic cancer showed a significantly higher frequency of positive glial cell line-derived neurotrophic factor (GDNF) immunostaining, and the intrapancreatic neural invasion by cancer cells was significantly related to the overexpression of GDNF (Zeng et al 2008). Importantly, a strongly positive expression of GDNF was significantly more frequent than lesser grades of GDNF expression in patients with pancreatic cancer (Zeng et al 2008).…”

Section: Introductionmentioning

confidence: 93%

“…Importantly, a recent report has shown that the severity of the neural invasion in rectal adenocarcinoma is an important factor in a scoring system to assess the prognostic value, showing high correlation with localization and severity (Ceyhan et al 2010). Patients with a surgically resected pancreatic cancer showed a significantly higher frequency of positive glial cell line-derived neurotrophic factor (GDNF) immunostaining, and the intrapancreatic neural invasion by cancer cells was significantly related to the overexpression of GDNF (Zeng et al 2008). Importantly, a strongly positive expression of GDNF was significantly more frequent than lesser grades of GDNF expression in patients with pancreatic cancer (Zeng et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

Huang

Chen

Chiu

et al. 2013

Endocrine-Related Cancer

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Glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophic factor, has been shown to affect cancer cell metastasis and invasion. However, the molecular mechanisms underlying GDNF-induced colon cancer cell migration remain unclear. GDNF is found to be positively correlated with malignancy in human colon cancer patients. The migratory activities of two human colon cancer cell lines, HCT116 and SW480, were found to be enhanced in the presence of human GDNF. The expression of vascular endothelial growth factor (VEGF) was also increased in response to GDNF stimulation, along with VEGF mRNA expression and transcriptional activity. The enhancement of GDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Our results also showed that the expression of VEGF receptor 1 (VEGFR1) was increased in response to GDNF stimulation, whereas GDNF-induced cancer cell migration was reduced by a VEGFR inhibitor. The GDNF-induced VEGF expression was regulated by the p38 and PI3K/Akt signaling pathways. Treatment with GDNF increased nuclear hypoxia-inducible factor 1 a (HIF1a) accumulation and its transcriptional activity in a time-dependent manner. Moreover, GDNF increased hypoxia responsive element (HRE)-containing VEGF promoter transcriptional activity but not that of the HRE-deletion VEGF promoter construct. Inhibition of HIF1a by a pharmacological inhibitor or dominant-negative mutant reduced the GDNF-induced migratory activity in human colon cancer cells. These results indicate that GDNF enhances the migration of colon cancer cells by increasing VEGF-VEGFR interaction, which is mainly regulated by the p38, PI3K/Akt, and HIF1a signaling pathways.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

Huang

Chen

Chiu

et al. 2013

Endocrine-Related Cancer

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“…RET oncogenic mutations contribute to cell transformation in medullary thyroid cancer (MTC) 2 (1). MTC occurs in sporadic (75%) or hereditary (25%) forms with three clinical subtypes: multiple endocrine neoplasia types 2A and 2B and familial MTC.…”

Section: Dent Inactivation Of Atf4 During the Pathogenesis Of Medullamentioning

confidence: 99%

“…Furthermore, RET overexpression has been observed in pancreatic cancer (2), melanoma (3), and leukemia (4). RET copy number gains, mutations, and rearrangements have been observed in breast cancer (5).…”

Section: Dent Inactivation Of Atf4 During the Pathogenesis Of Medullamentioning

confidence: 99%

A Novel Dual Kinase Function of the RET Proto-oncogene Negatively Regulates Activating Transcription Factor 4-mediated Apoptosis

Bagheri‐Yarmand

Sinha

Gururaj³

et al. 2015

Journal of Biological Chemistry

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Background: Activating mutations of the receptor tyrosine kinase RET are associated with oncogenic function in medullary thyroid cancer. Results: RET is a dual specificity kinase, phosphorylates ATF4, and inhibits expression of the ATF4 target proapoptotic genes. Conclusion: RET prevents apoptosis through inhibition of ATF4 activity. Significance: Simultaneous targeting of RET and ATF4 may provide clinical benefit in cancers with RET abnormalities.

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“…In another pancreatic cancer patient, an intronic L1 in the GDNF gene was also present in both the primary cancer and its metastasis. GDNF is a glial cell line-derived neurotrophic factor and a ligand of RET, which has been suggested to participate in pancreatic cancer progression and invasion (Zeng et al 2008). Intronic L1 insertions were likewise found in stomach tumors in the cancer driver candidate genes KLF12 (Kruppel-like factor 12), a known player in gastric cancer progression (Nakamura et al 2009), and in CTNND2, which encodes for catenin delta 2.…”

Section: Insertions In Known or Candidate Cancer Driver Genesmentioning

confidence: 99%

Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution

et al. 2015

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Somatic L1 retrotransposition events have been shown to occur in epithelial cancers. Here, we attempted to determine how early somatic L1 insertions occurred during the development of gastrointestinal (GI) cancers. Using L1-targeted resequencing (L1-seq), we studied different stages of four colorectal cancers arising from colonic polyps, seven pancreatic carcinomas, as well as seven gastric cancers. Surprisingly, we found somatic L1 insertions not only in all cancer types and metastases but also in colonic adenomas, well-known cancer precursors. Some insertions were also present in low quantities in normal GI tissues, occasionally caught in the act of being clonally fixed in the adjacent tumors. Insertions in adenomas and cancers numbered in the hundreds, and many were present in multiple tumor sections, implying clonal distribution. Our results demonstrate that extensive somatic insertional mutagenesis occurs very early during the development of GI tumors, probably before dysplastic growth.

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The Relationship between Over-expression of Glial Cell-derived Neurotrophic Factor and Its RET Receptor with Progression and Prognosis of Human Pancreatic Cancer

Cited by 69 publications

References 20 publications

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

GDNF increases cell motility in human colon cancer through VEGF–VEGFR1 interaction

A Novel Dual Kinase Function of the RET Proto-oncogene Negatively Regulates Activating Transcription Factor 4-mediated Apoptosis

Widespread somatic L1 retrotransposition occurs early during gastrointestinal cancer evolution

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