ELIZA

return kwic search for suggest out of >500 occurrences
308129 occurrences (No.71 in the rank) during 5 years in the PubMed. [cache]

18) Our findings indicate that calcineurin is a critical regulator of mitochondrial metabolism and suggest that CNIs may promote tumorigenesis through inhibition of the calcineurin-PDC pathway.

--- ABSTRACT ---

PMID:34667275 DOI:10.1038/s41388-021-02065-0

2021 Oncogene

* Calcineurin inactivation inhibits pyruvate dehydrogenase complex activity and induces the Warburg effect.

- Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase that connects the Ca²⁺-dependent signalling to multiple cellular responses. Calcineurin inhibitors (CNIs) have been widely used to suppress immune response in allograft patients. However, CNIs significantly increase cancer incidence in transplant recipients compared with the general population. Accumulating evidence suggests that CNIs may promote the malignant transformation of cancer cells in addition to its role in immunosuppression, but the underlying mechanisms remain poorly understood. Here, we show that calcineurin interacts with pyruvate dehydrogenase complex (PDC), a mitochondrial gatekeeper enzyme that connects two key metabolic pathways of cells, glycolysis and the tricarboxylic acid cycle. Mitochondrial-localized calcineurin dephosphorylates PDHA1 at Ser232, Ser293 and Ser300, and thus enhances PDC enzymatic activity, remodels cellular glycolysis and oxidative phosphorylation, and suppresses cancer cell proliferation. Hypoxia attenuates mitochondrial translocation of calcineurin to promote PDC inactivation. Moreover, CNIs promote metabolic remodelling and the Warburg effect by blocking calcineurin-mediated PDC activation in cancer cells. Our findings indicate that calcineurin is a critical regulator of mitochondrial metabolism and suggest that CNIs may promote tumorigenesis through inhibition of the calcineurin-PDC pathway.

--- ABSTRACT END ---

[
right
kwic]

[frequency of next (right) word to suggest]

(1)346 that	(4)6 an	(7)2 best	(10)2 integrating
(2)46 a	(5)6 that,	(8)2 either
(3)17 the	(6)3 ways	(9)2 further

add keyword

--- WordNet output for suggest --- =>〜しようと提案する, を提案する, 示唆する, 暗示する, 提案する Overview of verb suggest The verb suggest has 5 senses (first 5 from tagged texts) 1. (57) propose, suggest, advise -- (make a proposal, declare a plan for something; "the senator proposed to abolish the sales tax") 2. (21) hint, suggest -- (drop a hint; intimate by a hint) 3. (19) suggest, intimate -- (imply as a possibility; "The evidence suggests a need for more clarification") 4. (14) indicate, suggest -- (suggest the necessity of an intervention; in medicine; "Tetracycline is indicated in such cases") 5. (12) suggest, evoke, paint a picture -- (call to mind; "this remark evoked sadness") --- WordNet end ---