scholarly journals Corticotropin-Releasing Hormone Receptor Alters the Tumor Development and Growth in Apcmin/+ Mice and in a Chemically-Induced Model of Colon Cancer

2021 ◽  
Vol 22 (3) ◽  
pp. 1043
Author(s):  
Yunna Lee ◽  
Elise L. Ma ◽  
Marisa Patel ◽  
Gayoung Kim ◽  
Cody Howe ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Development ◽  
Human Colon ◽  
Mrna Levels ◽  
Corticotropin Releasing Hormone ◽  
Human Colon Cancer ◽  
Releasing Hormone ◽  
Normal Tissues ◽  
Chemically Induced ◽  
Cancer Tissues

The neuroendocrine circuit of the corticotropin-releasing hormone (CRH) family peptides, via their cognate receptors CRHR1 and CRHR2, copes with psychological stress. However, peripheral effects of the CRH system in colon cancer remains elusive. Thus, we investigate the role of CRHR1 and CRHR2 in colon cancer. Human colon cancer biopsies were used to measure the mRNA levels of the CRH family by quantitative real-time PCR. Two animal models of colon cancer were used: Apcmin/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. The mRNA levels of CRHR2 and UCN III are reduced in human colon cancer tissues compared to those of normal tissues. Crhr1 deletion suppresses the tumor development and growth in Apcmin/+ mice, while Crhr2 deficiency exacerbates the tumorigenicity. Crhr1 deficiency not only inhibits the expression of tumor-promoting cyclooxygenase 2, but also upregulates tumor-suppressing phospholipase A2 in Apcmin/+ mice; however, Crhr2 deficiency does not change these expressions. In the AOM/DSS model, Crhr2 deficiency worsens the tumorigenesis. In conclusion, Crhr1 deficiency confers tumor-suppressing effects in Apcmin/+ mice, but Crhr2 deficiency worsens the tumorigenicity in both Apcmin/+ and AOM/DSS-treated mice. Therefore, pharmacological inhibitors of CRHR1 or activators of CRHR2 could be of significance as anti-colon cancer drugs.

scholarly journals Knockdown of Forkhead box A1 suppresses the tumorigenesis and progression of human colon cancer cells through regulating the phosphatase and tensin homolog/Akt pathway

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052097145
Author(s):  
Jie Pan ◽  
Zongbin Xu ◽  
Meifang Xu ◽  
Xiaoyan Lin ◽  
Bingqiang Lin ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
Migration And Invasion ◽  
Human Colon Cancer ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Forkhead Box ◽  
Mrna And Protein Expression ◽  
Cancer Tissues ◽  
Foxa1 Expression

Background This study aimed to evaluate the role and the underlying mechanisms of Forkhead box A1 (encoded by FOXA1) in colon cancer. Methods We analyzed FOXA1 mRNA and protein expression in colon cancer tissues and cell lines. We also silenced FOXA1 expression in HCT116 and SW480 cells to evaluate the effects on cell proliferation, cell cycle, migration, and invasion by using MTT, colony formation, flow cytometry, and the Transwell assay, respectively. Results FOXA1 immunostaining was higher in colon cancer tissues than adjacent healthy tissues. FOXA1 mRNA and protein expression was significantly increased in human colon cancer cells compared with a normal colonic cell line. FOXA1 expression was also significantly higher in colorectal cancer tissues from TCGA data sets and was associated with worse prognosis in the R2 database. FOXA1 expression was negatively correlated with the extent of its methylation, and its knockdown reduced proliferation, migration, and invasion, and induced G2/M phase arrest in HCT116 and SW480 cells by suppressing the phosphatase and tensin homolog/Akt signaling pathway and inhibiting epithelial–mesenchymal transition. Conclusion FOXA1 may act as an oncogene in colon cancer tumorigenesis and development.

Alterations of O-glycan biosynthesis in human colon cancer tissues

Glycobiology ◽  
1994 ◽  
Vol 4 (6) ◽  
pp. 873-884 ◽  
Author(s):  
Ji-Mao Yang ◽  
James C. Byrd ◽  
Bader B. Siddiki ◽  
Yong-Suk Chung ◽  
Masahiro Okuno ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Cancer Tissues

scholarly journals Enhanced 4-Hydroxynonenal Resistance inKEAP1Silenced Human Colon Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Kyeong-Ah Jung ◽  
Mi-Kyoung Kwak
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Target Gene ◽  
Human Colon ◽  
Adduct Formation ◽  
Mrna Levels ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Ht29 Cells ◽  
Human Colon Cancer Cells

Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense. The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus. In the present study, we aimed to investigate the effect ofKEAP1knockdown on NRF2 target gene expression and its toxicological implication using human colon cancer cells. The stableKEAP1-knockdown HT29 cells exhibit elevated levels of NRF2 and its target gene expressions. In particular, the mRNA levels of aldo-keto reductases (AKR1C1, 1C2, 1C3, 1B1, and 1B10) were substantially increased inKEAP1silenced HT29 cells. These differential AKRs expressions appear to contribute to protection against oxidative stress. TheKEAP1-knockdown cells were relatively more resistant to hydrogen peroxide (H2O2) and 4-hydroxynonenal (4HNE) compared to the control cells. Accordantly, we observed accumulation of 4HNE protein adducts in H2O2- or 4HNE-treated control cells, whereasKEAP1-knockdown cells did not increase adduct formation. The treatment ofKEAP1-silenced cells with AKR1C inhibitor flufenamic acid increased 4HNE-induced cellular toxicity and protein adduct formation. Taken together, these results indicate that AKRs, which are NRF2-dependent highly inducible gene clusters, play a role in NRF2-mediated cytoprotection against lipid peroxide toxicity.

scholarly journals cis-Golgi resident proteins and O-glycans are abnormally compartmentalized in the RER of colon cancer cells

1993 ◽  
Vol 105 (3) ◽  
pp. 819-830 ◽  
Author(s):  
G. Egea ◽  
C. Franci ◽  
G. Gambus ◽  
T. Lesuffleur ◽  
A. Zweibaum ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Golgi Apparatus ◽  
Cancer Cells ◽  
Neoplastic Transformation ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Normal Colon ◽  
Human Colon Cancer ◽  
Protein Disulphide Isomerase ◽  
Cancer Tissues

Neoplastic transformation is commonly associated with altered glycosylation of proteins and lipids. To understand the basis for altered mucin glycosylation, we have examined the distribution of RER markers, a cis-Golgi resident protein, and the GalNAc alpha-O-Ser/Thr epitope (Tn) in human colon cancer cells and in normal colon. In cultured mucin-producing colon cancer cells, Gal-NAc alpha-O-Ser/Thr was found in mucin droplets and in RER cisternae. In addition, the Golgi apparatus was disorganized in a proportion of cells and a 130 kDa cis-Golgi resident protein was also abnormally redistributed to the RER. The distribution of the MUC2 intestinal apomucin, protein disulphide isomerase, Gal-NAc alpha-O-Ser/Thr, and the 130 kDa cis-Golgi resident protein was analysed in normal colon and in colon cancer tissues. In normal colon, MUC2 apomucin and protein disulphide isomerase were located in the RER, whereas the cis-Golgi resident protein and GalNAc alpha-O-Ser/Thr were detected only in the cis-Golgi compartment. In contrast, the two Golgi markers colocalized with the MUC2 apomucin and protein disulphide isomerase in the RER of colon cancer cells. On the basis of these results, we propose that in colon cancer cells a redistribution of molecules normally present in the Golgi apparatus takes place; this alteration may contribute to the abnormal glycosylation of proteins and lipids associated with neoplastic transformation.

scholarly journals β-Catenin/TCF4 Complex-Mediated Induction of the NRF3 (NFE2L3) Gene in Cancer Cells

2019 ◽  
Vol 20 (13) ◽  
pp. 3344 ◽  
Author(s):  
Shiori Aono ◽  
Ayari Hatanaka ◽  
Atsushi Hatanaka ◽  
Yue Gao ◽  
Yoshitaka Hippo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Glucose Transporter ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Genome Database ◽  
Related Transcription Factor ◽  
Cancer Tissues

Remarkable upregulation of the NRF2 (NFE2L2)-related transcription factor NRF3 (NFE2L3) in several cancer tissues and its correlation with poor prognosis strongly suggest the physiological function of NRF3 in tumors. Indeed, we had recently uncovered the function of NRF3, which promotes cancer cell proliferation by p53 degradation via the 20S proteasome. Nevertheless, the molecular mechanism underlying the induction of NRF3 gene expression in cancer cells is highly elusive. We herein describe that NRF3 upregulation is induced by the β-catenin/TCF4 complex in colon cancer cells. We first confirmed high NRF3 mRNA expression in human colon cancer specimens. The genome database indicated that the human NRF3 gene possesses a species-conserved WRE sequence (TCF/LEF consensus element), implying that the β-catenin/TCF complex activates NRF3 expression in colon cancer. Consistently, we observed that the β-catenin/TCF4 complex mediates NRF3 expression by binding directly to the WRE site. Furthermore, inducing NRF3 activates cell proliferation and the expression of the glucose transporter GLUT1. The existence of the β-catenin/TCF4-NRF3 axis was also validated in the intestine and organoids of Apc-deficient mice. Finally, the positive correlation between NRF3 and β-catenin target gene expression strongly supports our conclusion. Our findings clearly demonstrate that NRF3 induction in cancer cells is controlled by the Wnt/β-catenin pathway.

Ratiometric Detection of γ-Glutamyltransferase in Human Colon Cancer Tissues Using a Two-Photon Probe

2019 ◽  
Vol 91 (14) ◽  
pp. 9246-9250 ◽  
Author(s):  
Yun Ji Kim ◽  
Sang Jun Park ◽  
Chang Su Lim ◽  
Dong Jun Lee ◽  
Choong-Kyun Noh ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Two Photon ◽  
Ratiometric Detection ◽  
Cancer Tissues

Two-photon probes for pH: Detection of human colon cancer using two-photon microscopy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 607-607
Author(s):  
Woojung Kim ◽  
Eun Sun Kim ◽  
Geeho Min ◽  
Seung Han Kim ◽  
Seong ji Choi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Two Photon ◽  
Cancer Tissues ◽  
Hct116 Cells

607 Background: In cancer cells, lysosomal pH decreases along with a concomitant increase in lysosomal volume and cathepsin expression levels. Lysosomes also play crucial roles in cancer progression following their release into the extracellular space. Since cancer cells invade a tissue by secreting degradative enzymes, the extracellular pH of tumor tissues becomes acidic. However, to date, there has been no report on the use of multi-photon microscopy (MPM) probes to image human colon cancer tissues. Methods: We have developed multi-photon (MP) pH-sensitive probes (BH-2 and BHEt-1) that exhibit absorption and emission maxima at 370 and 466 nm, and TP absorption cross-section values of 51 and 61 GM (1 GM = 10−50 cm4 s/photon), respectively, at 750 nm and pH 3.0 in a universal buffer (0.1 M citric acid, 0.1 M KH2PO4, 0.1 M Na2B4O7, 0.1 M Tris, 0.1 M KCl)/1,4-dioxane (7/ 3) solution. Results: The TPM images of CCD-18co (a normal colon cell line) and HCT116 cells (a colon cancer cell line) labeled with BH-2 were too dim to be distinguished. When the same cells were labeled with BHEt-1, however, the MPM image of the HCT116 cells was much brighter than that of CCD-18co cells, and the relative proportion of the acidic vesicles (Pacid) of the former was 5-fold larger than that of latter. BHEt-1 could also differentiate HepG2 cells (a human liver cancer cell line) from LX-2 cells (a human hepatic stellate cell line) with a 6-fold larger P acid value. Human colon cancer tissues labeled with BHEt-1 showed similar results, demonstrating much brighter MPM images and 6-fold larger Pacid values compared to normal tissue. Conclusions: These results suggest the potential utility of BHEt-1 for molecular image analysis of colon cancer tissues using MPM.

scholarly journals Increased Expression of TRPS1 Affects Tumor Progression and Correlates with Patients' Prognosis of Colon Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Jun Hong ◽  
Jie Sun ◽  
Tao Huang
Keyword(s):  
Colon Cancer ◽  
Cox Regression ◽  
Mrna Level ◽  
Human Colon ◽  
Positive Lymph Node ◽  
Human Colon Cancer ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Potential Marker ◽  
Cancer Tissues

Aim. To detect the expression pattern of tricho-rhino-phalangeal syndrome-1 (TRPS1) in human colon cancer and to analyze its correlation with prognosis of patients with this disease.Methods. The expressions of TRPS1 in human colon cancer and its corresponding noncancerous colon tissues were detected at both mRNA and protein levels.Results. The mRNA and protein expression levels of TRPS1 were both significantly higher in colon cancer than in corresponding noncancerous colon tissues (bothP<0.001). The protein level of TRPS1 in colon cancer tissues was significantly correlated with the mRNA level (r=0.9,P<0.001). Additionally, immunohistochemistry analysis also found increased TRPS1 expression in 63.0% (63/100) of colon cancer tissues. High TRPS1 expression was significantly associated with positive lymph node metastasis (P=0.006) and higher pathological stage (P=0.008) of patients with colon cancer. Multivariate Cox regression analysis further suggested that the increased expression of TRPS1 was an independent poor prognostic factor for this disease.Conclusion. Our data offer the convincing evidence for the first time that the increased expression of TRPS1 may be involved in the pathogenesis and progression of colon cancer. TRPS1 might be a potential marker to predict the prognosis in colon cancer.

Human Colon Cancer Tissues Are More Sensitive than Rectal Cancer Tissues to Antitumor Drugs in vitro

Oncology ◽  
1991 ◽  
Vol 48 (2) ◽  
pp. 158-161 ◽  
Author(s):  
Hiroaki Ueo ◽  
Yoshihiko Maehara ◽  
Atsushi Saito ◽  
Yoshihisa Sakaguchi ◽  
Shunji Kohnoe ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Human Colon ◽  
Antitumor Drugs ◽  
Human Colon Cancer ◽  
Cancer Tissues
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