2021 Proceedings of the National Academy of Sciences of the United States of America
* NAD+ depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition.
- Emerging evidence suggests that intratumoral interferon (IFN) signaling can trigger targetable vulnerabilities. A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its extensively reprogrammed metabolic network, in which nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are critical cofactors. Here, we show that IFN signaling, present in a subset of PDAC tumors, substantially lowers NAD(H) levels through up-regulating the expression of NAD-consuming enzymes PARP9, PARP10, and PARP14. Their individual contributions to this mechanism in PDAC have not been previously delineated. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD salvage pathway, a dominant source of NAD in cancer cells. We found that IFN-induced NAD consumption increased dependence upon NAMPT for its role in recycling NAM to salvage NAD pools, thus sensitizing PDAC cells to pharmacologic NAMPT inhibition. Their combination decreased PDAC cell proliferation and invasion in vitro and suppressed orthotopic tumor growth and liver metastases in vivo.
=>価格を評定する, 割合, 率, 歩合, 料金, 値段, 相場, 速度, 度合, 人を〜を思う, みなす, 価値がある,
人を〜とみなす, 科金, 評価する
Overview of noun rate
The noun rate has 4 senses (first 3 from tagged texts)
1. (68) rate -- (a magnitude or frequency relative to a time unit; "they traveled at a rate of 55
miles per hour"; "the rate of change was faster than expected")
2. (39) rate, charge per unit -- (amount of a charge or payment relative to some basis; "a 10-minute
phone call at that rate would cost $5")
3. (1) pace, rate -- (the relative speed of progress or change; "he lived at a fast pace"; "he works
at a great rate"; "the pace of events accelerated")
4. rate -- (a quantity or amount or measure considered as a proportion of another quantity or amount
or measure; "the literacy rate"; "the retention rate"; "the dropout rate")
Overview of verb rate
The verb rate has 3 senses (first 3 from tagged texts)
1. (9) rate, rank, range, order, grade, place -- (assign a rank or rating to; "how would you rank
these students?"; "The restaurant is rated highly in the food guide")
2. (2) rate -- (be worthy of or have a certain rating; "This bond rates highly")
3. (1) rate, value -- (estimate the value of; "How would you rate his chances to become President?";
"Gold was rated highly among the Romans")
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