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The role of Reg IV in colorectal cancer, as a potential therapeutic target.

Hu Y, Pan C, Hu J, Zhang S - Contemp Oncol (Pozn) (2015)

Bottom Line: Reg IV overexpression in tumor cells has been associated with carcinogenesis, tissue regeneration, proliferation and resistance to apoptosis.Reg IV treatment inhibits 5-fluorouracil induced apoptosis, at least two mechanisms are involved in inhibition of apoptosis by Reg IV, including Bcl-2 and dihydropyrimidine dehydrogenase (DPD).Recently, one proteoglycan was confirmed to disrupt this signaling pathway to perform antitumor effect.

View Article: PubMed Central - PubMed

Affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), School of Medicine, Zhejiang University, Hangzhou, PR China.

ABSTRACT
Regenerating islet-derived family, member 4 (Reg IV), a member of the Reg gene family, has been reported to be overexpressed in gastrointestinal tract cancers. Reg IV overexpression in tumor cells has been associated with carcinogenesis, tissue regeneration, proliferation and resistance to apoptosis. Reg IV activates the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer and increases expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), which are associated with the inhibition of apoptosis, results in mitogenic signaling in colon cancer cells, increase cell proliferation, metastasis and decreased apoptosis. Reg IV treatment inhibits 5-fluorouracil induced apoptosis, at least two mechanisms are involved in inhibition of apoptosis by Reg IV, including Bcl-2 and dihydropyrimidine dehydrogenase (DPD). These studies may lead to novel therapeutic strategies for cancers expressing Reg IV. Recently, one proteoglycan was confirmed to disrupt this signaling pathway to perform antitumor effect. This review summaries current knowledge of the expression and roles of Reg IV in human colorectal cancer, describes the possible signaling pathway which Reg IV activates, and discusses the relevance of Reg IV as a potential therapeutic target for cancer treatment.

No MeSH data available.


Related in: MedlinePlus

Reg IV activates the EGFR/Akt/AP-1 signaling pathway. Regenerating islet-derived type IV (Reg IV) could activate the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer cells and increases expression of Bcl-xl and Bcl-2, resulting in cell proliferation and inhibition of apoptosis. B-cell lymphoma-2 prevents mitochondrial membrane permeabilization and leads to 5-FU resistance. Dihydropyrimidine dehydrogenase is an initial and rate-limiting enzyme in 5-FU catabolism, which can be induced by AP-1
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Figure 0001: Reg IV activates the EGFR/Akt/AP-1 signaling pathway. Regenerating islet-derived type IV (Reg IV) could activate the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer cells and increases expression of Bcl-xl and Bcl-2, resulting in cell proliferation and inhibition of apoptosis. B-cell lymphoma-2 prevents mitochondrial membrane permeabilization and leads to 5-FU resistance. Dihydropyrimidine dehydrogenase is an initial and rate-limiting enzyme in 5-FU catabolism, which can be induced by AP-1

Mentions: Li et al. suggested that a proteoglycan named ‘P1’ which is from Phellinus linteus (PL) could disrupt the Reg IV/EGFR/Akt/AP-1 signaling pathway [35] (Fig. 1). They found that treatment of colonic adenocarcinoma cells with P1 resulted in significant dose-dependent inhibition in cell numbers and cell mitosis. P1 had the capacity to downregulate the expression of Reg IV and EGFR. Therefore, the proteoglycan P1 was considered to block the EGFR signaling pathway and induce Reg IV downregulation. Also, a study in vivo confirmed this hypothesis. P1 has a direct antitumor effect through inducing apoptosis and inhibiting the karyokinesis of HT-29 cells. The results are consistent with the previous report by Li et al. [36]. Therefore we expect that it will be possible to use P1 as an adjuvant chemotherapeutic and chemopreventive agent. Numerous proteins in the Reg IV/EGFR/Akt/AP-1 signaling pathway are potential therapeutic targets for colorectal cancer treatment awaiting discovery.


The role of Reg IV in colorectal cancer, as a potential therapeutic target.

Hu Y, Pan C, Hu J, Zhang S - Contemp Oncol (Pozn) (2015)

Reg IV activates the EGFR/Akt/AP-1 signaling pathway. Regenerating islet-derived type IV (Reg IV) could activate the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer cells and increases expression of Bcl-xl and Bcl-2, resulting in cell proliferation and inhibition of apoptosis. B-cell lymphoma-2 prevents mitochondrial membrane permeabilization and leads to 5-FU resistance. Dihydropyrimidine dehydrogenase is an initial and rate-limiting enzyme in 5-FU catabolism, which can be induced by AP-1
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631303&req=5

Figure 0001: Reg IV activates the EGFR/Akt/AP-1 signaling pathway. Regenerating islet-derived type IV (Reg IV) could activate the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer cells and increases expression of Bcl-xl and Bcl-2, resulting in cell proliferation and inhibition of apoptosis. B-cell lymphoma-2 prevents mitochondrial membrane permeabilization and leads to 5-FU resistance. Dihydropyrimidine dehydrogenase is an initial and rate-limiting enzyme in 5-FU catabolism, which can be induced by AP-1
Mentions: Li et al. suggested that a proteoglycan named ‘P1’ which is from Phellinus linteus (PL) could disrupt the Reg IV/EGFR/Akt/AP-1 signaling pathway [35] (Fig. 1). They found that treatment of colonic adenocarcinoma cells with P1 resulted in significant dose-dependent inhibition in cell numbers and cell mitosis. P1 had the capacity to downregulate the expression of Reg IV and EGFR. Therefore, the proteoglycan P1 was considered to block the EGFR signaling pathway and induce Reg IV downregulation. Also, a study in vivo confirmed this hypothesis. P1 has a direct antitumor effect through inducing apoptosis and inhibiting the karyokinesis of HT-29 cells. The results are consistent with the previous report by Li et al. [36]. Therefore we expect that it will be possible to use P1 as an adjuvant chemotherapeutic and chemopreventive agent. Numerous proteins in the Reg IV/EGFR/Akt/AP-1 signaling pathway are potential therapeutic targets for colorectal cancer treatment awaiting discovery.

Bottom Line: Reg IV overexpression in tumor cells has been associated with carcinogenesis, tissue regeneration, proliferation and resistance to apoptosis.Reg IV treatment inhibits 5-fluorouracil induced apoptosis, at least two mechanisms are involved in inhibition of apoptosis by Reg IV, including Bcl-2 and dihydropyrimidine dehydrogenase (DPD).Recently, one proteoglycan was confirmed to disrupt this signaling pathway to perform antitumor effect.

View Article: PubMed Central - PubMed

Affiliation: Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), School of Medicine, Zhejiang University, Hangzhou, PR China.

ABSTRACT
Regenerating islet-derived family, member 4 (Reg IV), a member of the Reg gene family, has been reported to be overexpressed in gastrointestinal tract cancers. Reg IV overexpression in tumor cells has been associated with carcinogenesis, tissue regeneration, proliferation and resistance to apoptosis. Reg IV activates the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer and increases expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), which are associated with the inhibition of apoptosis, results in mitogenic signaling in colon cancer cells, increase cell proliferation, metastasis and decreased apoptosis. Reg IV treatment inhibits 5-fluorouracil induced apoptosis, at least two mechanisms are involved in inhibition of apoptosis by Reg IV, including Bcl-2 and dihydropyrimidine dehydrogenase (DPD). These studies may lead to novel therapeutic strategies for cancers expressing Reg IV. Recently, one proteoglycan was confirmed to disrupt this signaling pathway to perform antitumor effect. This review summaries current knowledge of the expression and roles of Reg IV in human colorectal cancer, describes the possible signaling pathway which Reg IV activates, and discusses the relevance of Reg IV as a potential therapeutic target for cancer treatment.

No MeSH data available.


Related in: MedlinePlus