<i>Gas1</i> Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma

Li, Qingguo; Qin, Yi; Wei, Ping; Lian, Peng; Li, Yaqi; Xu, Ye; Li, Xinxiang; Li, Dawei; Cai, Sanjun

doi:10.1158/1541-7786.mcr-16-0032

Cited by 61 publications

(67 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in agreement with other studies demonstrating that Gas1 is capable of initiating apoptosis and inhibiting proliferation [70, 71]. Interestingly, Gas1 exerts similar functions in oncogenesis [63, 72]. Gas1 activity detains tumour growth by inhibiting the proliferation of breast cancer cells [63] and has been reported to play the same mechanistic role in a variety of other cancers; such as colorectal carcinoma [72], papillary thyroid carcinoma [64] and glioma [70].…”

Section: Discussionsupporting

confidence: 92%

“…Interestingly, Gas1 exerts similar functions in oncogenesis [63, 72]. Gas1 activity detains tumour growth by inhibiting the proliferation of breast cancer cells [63] and has been reported to play the same mechanistic role in a variety of other cancers; such as colorectal carcinoma [72], papillary thyroid carcinoma [64] and glioma [70]. In Gas −/− ; Boc −/− PS the CPI was restored to levels observed in Gas +/− ; Boc +/− suggesting that the two genes have opposing roles in regulating cell density.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic interactions between the hedgehog co-receptorsGas1andBocregulate cell proliferation during murine palatogenesis

et al. 2016

View full text Add to dashboard Cite

Abnormal regulation of Sonic hedgehog (Shh) signaling has been described in a variety of human cancers and developmental anomalies, which highlights the essential role of this signaling molecule in cell cycle regulation and embryonic development. Gas1 and Boc are membrane co-receptors for Shh, which demonstrate overlapping domains of expression in the early face. This study aims to investigate potential interactions between these co-receptors during formation of the secondary palate. Mice with targeted mutation in Gas1 and Boc were used to generate Gas1; Boc compound mutants. The expression of key Hedgehog signaling family members was examined in detail during palatogenesis via radioactive in situ hybridization. Morphometric analysis involved computational quantification of BrdU-labeling and cell packing; whilst TUNEL staining was used to assay cell death. Ablation of Boc in a Gas1 mutant background leads to reduced Shh activity in the palatal shelves and an increase in the penetrance and severity of cleft palate, associated with failed elevation, increased proliferation and reduced cell death. Our findings suggest a dual requirement for Boc and Gas1 during early development of the palate, mediating cell cycle regulation during growth and subsequent fusion of the palatal shelves.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Genetic interactions between the hedgehog co-receptorsGas1andBocregulate cell proliferation during murine palatogenesis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…As positron emission tomography (PET) technology using 18F-fluoro-2-deoxyglucose (FDG) is a manifestation of glycolysis in vivo [16, 17], the SUVmax has been widely used as a surrogate marker for the prognosis of disease in numerous types of cancer, including gastric cancer [18]. To confirm the relationship between Snail and glucose metabolism, we further analyzed the correlation between the Snail IHC staining and the PET/CT SUVmax data from gastric cancer patients.…”

Section: Resultsmentioning

confidence: 99%

Snail Enhances Glycolysis in the Epithelial-Mesenchymal Transition Process by Targeting FBP1 in Gastric Cancer

Chen

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Snail is a key regulator of epithelial-mesenchymal transition (EMT) in cancer. However, the regulatory role and underlying mechanisms of Snail in gastric cancer metabolism are unknown. In this study, we characterized the regulation of aerobic glycolysis by Snail in gastric cancer. Methods: The impact of Snail on glucose metabolism was studied in vitro. Combining maximum standardized uptake value (SUVmax), which was obtained preoperatively via a PET/CT scan, with immunohistochemistry staining, we further analyzed the correlation between SUVmax and Snail expression in gastric cancer tissues. Results: Increased expression of Snail promoted lactate production, glucose utilization, and decreased FBP1 expression at both mRNA and protein level. The expression level of Snail was positively associated with SUVmax in gastric cancer patients (P=0.022). Snail and FBP1 expression were inversely correlated at both mRNA and protein level (P=0.002 and P=0.015 respectively) in gastric cancer tissues. Further studies demonstrated that Snail inhibited the FBP1 gene expression at the transcriptional level. Restoring FBP1 expression reversed the effects of glycolysis and EMT induced by Snail in gastric cancer cells. Conclusions: Our results thus reveal that Snail serves as a positive regulator of glucose metabolism through regulation of the FBP1 in gastric cancer. Disrupting the Snail-FBP1 signaling axis may be effective to prevent primary tumor EMT and glycolysis process.

show abstract

“…Some studies have demonstrated that glycolytic enzymes are involved in the EMT process, including FBP1 [10,11,22], PKM2 [23], and LDHA. Glycolytic enzymes are also regulated by classic EMT regulators [11,[24][25][26], so, it is not surprising that PGK1 can regulate the EMT process in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

Wei

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. Materials: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. Results: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P< 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P< 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P< 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. Conclusion: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer.

show abstract

Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma

Cited by 61 publications

References 40 publications

Genetic interactions between the hedgehog co-receptorsGas1andBocregulate cell proliferation during murine palatogenesis

Genetic interactions between the hedgehog co-receptorsGas1andBocregulate cell proliferation during murine palatogenesis

Snail Enhances Glycolysis in the Epithelial-Mesenchymal Transition Process by Targeting FBP1 in Gastric Cancer

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

Contact Info

Product

Resources

About