Pancreatic cancer: branched-chain amino acids as putative key metabolic regulators?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F21%3A00553167" target="_blank" >RIV/67985823:_____/21:00553167 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/21:43922710

Výsledek na webu

<a href="https://doi.org/10.1007/s10555-021-10016-0" target="_blank" >https://doi.org/10.1007/s10555-021-10016-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10555-021-10016-0" target="_blank" >10.1007/s10555-021-10016-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pancreatic cancer: branched-chain amino acids as putative key metabolic regulators?

Popis výsledku v původním jazyce

Branched-chain amino acids (BCAA) are essential amino acids utilized in anabolic and catabolic metabolism. While extensively studied in obesity and diabetes, recent evidence suggests an important role for BCAA metabolism in cancer. Elevated plasma levels of BCAA are associated with an increased risk of developing pancreatic cancer, namely pancreatic ductal adenocarcinoma (PDAC), a tumor with one of the highest 1-year mortality rates. The dreadful prognosis for PDAC patients could be attributable also to the early and frequent development of cancer cachexia, a fatal host metabolic reprogramming leading to muscle and adipose wasting. We propose that BCAA dysmetabolism is a unifying component of several pathological conditions, i.e., obesity, insulin resistance, and PDAC. These conditions are mutually dependent since PDAC ranks among cancers tightly associated with obesity and insulin resistance. It is also well-established that PDAC itself can trigger insulin resistance and new-onset diabetes. However, the exact link between BCAA metabolism, development of PDAC, and tissue wasting is still unclear. Although tissue-specific intracellular and systemic metabolism of BCAA is being intensively studied, unresolved questions related to PDAC and cancer cachexia remain, namely, whether elevated circulating BCAA contribute to PDAC etiology, what is the biological background of BCAA elevation, and what is the role of adipose tissue relative to BCAA metabolism during cancer cachexia. To cover those issues, we provide our view on BCAA metabolism at the intracellular, tissue, and whole-body level, with special emphasis on different metabolic links to BCAA intermediates and the role of insulin in substrate handling.

Název v anglickém jazyce

Pancreatic cancer: branched-chain amino acids as putative key metabolic regulators?

Popis výsledku anglicky

Branched-chain amino acids (BCAA) are essential amino acids utilized in anabolic and catabolic metabolism. While extensively studied in obesity and diabetes, recent evidence suggests an important role for BCAA metabolism in cancer. Elevated plasma levels of BCAA are associated with an increased risk of developing pancreatic cancer, namely pancreatic ductal adenocarcinoma (PDAC), a tumor with one of the highest 1-year mortality rates. The dreadful prognosis for PDAC patients could be attributable also to the early and frequent development of cancer cachexia, a fatal host metabolic reprogramming leading to muscle and adipose wasting. We propose that BCAA dysmetabolism is a unifying component of several pathological conditions, i.e., obesity, insulin resistance, and PDAC. These conditions are mutually dependent since PDAC ranks among cancers tightly associated with obesity and insulin resistance. It is also well-established that PDAC itself can trigger insulin resistance and new-onset diabetes. However, the exact link between BCAA metabolism, development of PDAC, and tissue wasting is still unclear. Although tissue-specific intracellular and systemic metabolism of BCAA is being intensively studied, unresolved questions related to PDAC and cancer cachexia remain, namely, whether elevated circulating BCAA contribute to PDAC etiology, what is the biological background of BCAA elevation, and what is the role of adipose tissue relative to BCAA metabolism during cancer cachexia. To cover those issues, we provide our view on BCAA metabolism at the intracellular, tissue, and whole-body level, with special emphasis on different metabolic links to BCAA intermediates and the role of insulin in substrate handling.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/NV19-01-00101" target="_blank" >NV19-01-00101: Nádor pankreatu: metabolické změny asociované s inzulínovou rezistencí</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cancer and Metastasis Reviews

ISSN

0167-7659

e-ISSN

1573-7233

Svazek periodika

40

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

25

Strana od-do

1115-1139

Kód UT WoS článku

000735340900001

EID výsledku v databázi Scopus

2-s2.0-85121865652