Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Nat Metab ; 5(12): 2131-2147, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37957387

ABSTRACT

Glutamine is a critical metabolite for rapidly proliferating cells as it is used for the synthesis of key metabolites necessary for cell growth and proliferation. Glutamine metabolism has been proposed as a therapeutic target in cancer and several chemical inhibitors are in development or in clinical trials. How cells subsist when glutamine is limiting is poorly understood. Here, using an unbiased screen, we identify ALDH18A1, which encodes P5CS, the rate-limiting enzyme in the proline biosynthetic pathway, as a gene that cells can downregulate in response to glutamine starvation. Notably, P5CS downregulation promotes de novo glutamine synthesis, highlighting a previously unrecognized metabolic plasticity of cancer cells. The glutamate conserved from reducing proline synthesis allows cells to produce the key metabolites necessary for cell survival and proliferation under glutamine-restricted conditions. Our findings reveal an adaptive pathway that cancer cells acquire under nutrient stress, identifying proline biosynthesis as a previously unrecognized major consumer of glutamate, a pathway that could be exploited for developing effective metabolism-driven anticancer therapies.


Subject(s)
Glutamine , Neoplasms , Humans , Glutamine/metabolism , Cell Proliferation , Proline , Glutamates
2.
J Oral Pathol Med ; 40(2): 135-42, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21073537

ABSTRACT

BACKGROUND: The presence of cancer stem cell (CSC) antigens can be evidenced in some human tumors by phenotypic analysis through immunostaining. This study aims to identify a putative CSC immunophenotype in oral squamous cell carcinoma (OSCC) and determine its influence on prognosis. METHODS: The following data were retrieved from 157 patents: age, gender, primary anatomic site, smoking and alcohol intake, recurrence, metastases, histologic classification, treatment, disease-free survival (DFS), and overall survival (OS). An immunohistochemical study for CD44 and CD24 was performed in a tissue microarray of 157 paraffin blocks of OSCCs. RESULTS: In univariate analysis, the immunostaining pattern showed significant influences in relation to OS for alcohol intake and treatment, as well as for the CD44(+) and CD44(-) /CD24(-) immunophenotypes. The multivariate test confirmed these associations. CONCLUSIONS: Based on our results, the CD44 immunostaining and the absence of immunoexpression of these two investigated markers can be used in combination with other clinicopathologic information to improve the assessment of prognosis in OSCC.


Subject(s)
Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/pathology , Neoplastic Stem Cells/pathology , Adult , Aged , Aged, 80 and over , CD24 Antigen/biosynthesis , Carcinoma, Squamous Cell/metabolism , Chi-Square Distribution , Female , Humans , Hyaluronan Receptors/biosynthesis , Immunophenotyping , Kaplan-Meier Estimate , Male , Middle Aged , Mouth Neoplasms/metabolism , Prognosis , Proportional Hazards Models , Survival Analysis , Tissue Array Analysis
SELECTION OF CITATIONS
SEARCH DETAIL
...