Mechanism of Cancer Cell Adaptation to Metabolic Stress

Li, Rui; Li, Zhenjun; Bai, Shujun; Zhang, Haiyuan; Tang, Minghai; Y, Lei; Chen, Lijuan; Liang, Shufang; Zhao, Ying; Wei, Yuquan; Huang, Canhua

doi:10.1074/mcp.m800195-mcp200

Cited by 64 publications

(31 citation statements)

References 47 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of TALDO1 is accompanied by a decrease in glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities, a concomitant depletion in NADPH and GSH levels, and increased sensitivity to apoptosis provoked by serum deprivation, H2O2, nitric oxide, TNF, and anti-Fas monoclonal antibody [24,33]. In support of this, TALDO1 overexpression has been observed in gastric cancer by proteomic approaches [25]. This study was the first identification of TALDO1 overexpression in CRC, and its precise role in carcinogenesis needs further investigation.…”

Section: Discussionmentioning

confidence: 73%

“…However, the underlying mechanism remains poorly defined [35,36]. TH overexpression has been observed in gastric cancer by proteomic approaches [25]. This study was the first identification of thyroid receptor interactor down-regulation in CRC, and its precise role in carcinogenesis needs further investigation.…”

Section: Discussionmentioning

confidence: 94%

“…Two of these proteins, Transaldolase 1 (TALDO1) and thyroid receptor interactor, are key carcinogenesis-associated molecules in the mechanism of cancer cell adaptation to metabolic stress, [24,25] and these were therefore chosen for validation and analysis. The data presented in this study suggest that TALDO1 and thyroid receptor interactor may be biomarkers for early diagnosis, prognosis, and monitoring in the therapy of CRC.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Searching for serum tumor markers for colorectal cancer using a 2‐D DIGE approach

Peng

Huang

et al. 2009

Electrophoresis

View full text Add to dashboard Cite

Identification of specific protein markers for colorectal cancer (CRC) could provide a basis for its early diagnosis and detection, as well as clues to the molecular mechanisms governing cancer progression. In the present study, 2-D DIGE coupled with MS was used to screen for biomarker candidates in the serum proteome of ten human CRC samples and ten healthy control samples. After pooling identical amounts of serum proteins (based on total protein concentration), albumin/IgG was depleted under partially denaturing conditions. Subsequently, the serum samples were labeled with three different CyDyes, and separated by 2-D DIGE. After analysis with the biological variation analysis module of the DeCyder software, only three spots were found to be significantly elevated in all patient groups (with ratios from 1.52 to 9.08), whereas five spots were significantly down-regulated in patients (with ratios from -1.23 to -10.21) (t-test; p<0.05). Finally, two potential biomarkers, Transaldolase 1 and thyroid receptor interactor, were chosen for validation and analysis by ELISA with the serum of 30 CRC patients and 30 healthy controls. The serum levels of the two proteins correlated well with the 2-D DIGE results. Thus, 2-D DIGE approaches show great promise for biomarker discovery in CRC.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Searching for serum tumor markers for colorectal cancer using a 2‐D DIGE approach

Peng

Huang

et al. 2009

Electrophoresis

View full text Add to dashboard Cite

show abstract

“…Recently, oxidative stress appeared to be involved in the regulation of various physiological and pathological processes, including tumor metastasis [21][22][23]. Thus we next set out to determine if ROS has a role in low-concentration capsaicin-induced metastasis of CRC cells.…”

Section: Low-concentration Capsaicin-induced Metastasis Of Crc Cells mentioning

confidence: 99%

Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways

Yang

Li²,

Xu³

et al. 2013

neo

100

View full text Add to dashboard Cite

Colorectal cancer (CRC), one of the most common human malignancies, is a major public health problem in the developed world. Capsaicin, widely used as a food additive and as an analgesic agent, is a major pungent ingredient of red pepper. Though capsaicin-induced apoptosis was previously reported in cancer cells, relatively little is known about the impact of capsaicin on other aspect of cancer cell behavior. In this study, we demonstrated that treatment with high-concentration of capsaicin (≥ 200 µM for SW480 and CT-26 cell lines; ≥ 25 µM for HCT116 cell line) inhibited CRC cell proliferation in a dose-dependent manner. In spite of no anti-proliferative effect, notably, low-concentration of capsaicin (100 µM for SW480 and CT-26 cell lines; 12.5 µM for HCT116 cell line) enhanced both migratory and invasive capability of these cells, which was validated by both in vitro and in vivo model. Further, we showed that 100 µM capsaicin induced epithelial-to-mesenchymal (EMT), up-regulated expression of MMP-2 and MMP-9, and activated Akt/mTOR and STAT-3 pathways in SW480 cells. Finally, we showed that capsaicin-induced metastasis of CRC cells was mediated by modulating reactive oxygen species (ROS) production. Our findings are considered as a significant step toward a better understanding of capsaicin-associated regulatory network on CRC cells.

show abstract

“…Fumarate itself inhibits HIF prolyl 4-hydroxylases and consequently stabilizes hypoxia-inducible factor (HIF)-1␣, a key regulator of tumor metabolism (23,24,26,27). Specifically, germline mutations of fumarase, an enzyme in the Krebs cycle that converts fumarate to malate, increase fumarate concentrations, and predispose individuals to multiple leiomyomas, testicular tumors, and hereditary leiomyomatosis renal cell cancer (HLRCC) (23, 24, 28 -30).…”

Section: Discussionmentioning

confidence: 99%

Intracellular Succinylation of 8-Chloroadenosine and Its Effect on Fumarate Levels

Dennison

Ayres

Kaluarachchi

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

8-Chloroadenosine (8-Cl-Ado) is a ribosyl nucleoside analog currently in phase I testing for the treatment of chronic lymphocytic leukemia (CLL). 8-Cl-Ado activity is dependent on adenosine kinase and requires intracellular accumulation of 8-Cl-Ado as mono-, di-, and tri-phosphates. In the current study with four mantle cell lymphoma cell lines, we report a new major metabolic pathway for 8-Cl-Ado intracellular metabolism, the formation of succinyl-8-chloro-adenosine (S-8-Cl-Ado) and its monophosphate (S-8-Cl-AMP). 8-Cl-AMP levels were highly associated with S-8-Cl-AMP levels and reached a steady-state prior to the secondary metabolites, 8-Cl-ATP and S-8-Cl-Ado. Consistent with fumarate as a required substrate for formation of succinyl-8-Cl-adenylate metabolites, the S-8-Cl-adenylate concentrations in multiple cell lines were associated with fumarate loss. The distribution of metabolites was also altered using the energy metabolism modifiers, metformin and oligomycin. The rates of succinyl-8-Cl-adenylate metabolism were enhanced by increasing the intracellular fumarate concentrations after metformin co-treatment. In addition, the S-8-Cl-AMP concentrations were increased after acute inhibition of ATP synthase by oligomycin. We conclude that 8-Cl-Ado metabolism not only affects intracellular purine metabolism; 8-Cl-Ado conversion to succinyl analogs ties its metabolism to the citric acid cycle by reduction of the fumarate pool. 8-Chloroadenosine (8-Cl-Ado)3 is a purine nucleoside analog with reported preclinical activity in multiple hematological malignancies (1-3). Currently 2, 3) or by incorporating into the poly(A)tail of mRNA transcripts, which is required for functionality and stability of the transcripts (9). Subsequent apoptosis is promoted by reduced expression of short-lived survival proteins, such as Mcl-1 in CLL and MET in multiple myeloma (4, 6). In addition, intracellular 8-Cl-ADP competes with ADP for mitochondrial ATP synthase and consequently reduces intracellular ATP concentrations (10). 8-Cl-Ado phosphorylated metabolites may also inhibit ribonucleotide reductase and reduce dATP levels causing an imbalance of the dNTP pool (1).As previously described, the mechanisms of action for 8-ClAdo have focused on phosphorylated metabolites, in particular 8-Cl-ATP, as the primary active intracellular metabolites. However, as with normal adenosine metabolism, 8-Cl-Ado may be a precursor not just for its mono-, di-, and tri-phosphate nucleotides but for multiple metabolic conjugates including nicotinamide adenine dinucleotide (NAD), S-adenosyl methionine (SAM), and flavin adenine dinucleotide (FAD). In the current study, we identified two new major 8-Cl-Ado metabolites, but the metabolites were not the downstream products we predicted. Instead, 8-Cl-Ado was metabolized to adenosine precursor molecules, succinyl-conjugated metabolites: succinyl-8-chloro-adenosine (S-8-Cl-Ado) and succinyl-8-chloro-AMP (S-8-Cl-AMP). Whereas the loss of ATP has already been associated with 8-Cl-ATP formation (1, 2, 5), this new...

show abstract

Mechanism of Cancer Cell Adaptation to Metabolic Stress

Cited by 64 publications

References 47 publications

Searching for serum tumor markers for colorectal cancer using a 2‐D DIGE approach

Searching for serum tumor markers for colorectal cancer using a 2‐D DIGE approach

Low-concentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways

Intracellular Succinylation of 8-Chloroadenosine and Its Effect on Fumarate Levels

Contact Info

Product

Resources

About