Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity.
Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity.
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DOI：
10.1038/s41389-021-00373-4
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发表时间：
2021-11-29
期刊：
影响因子：
6.2
通讯作者：
Savkovic SD
中科院分区：
文献类型：
--
作者：
Iftikhar R;Penrose HM;King AN;Samudre JS;Collins ME;Hartono AB;Lee SB;Lau F;Baddoo M;Flemington EF;Crawford SE;Savkovic SD
Obesity is a worldwide epidemic associated with increased risk and progression of colon cancer. Here, we aimed to determine the role of adipose triglyceride lipase (ATGL), responsible for intracellular lipid droplet (LD) utilization, in obesity-driven colonic tumorigenesis. In local colon cancer patients, significantly increased ATGL levels in tumor tissue, compared to controls, were augmented in obese individuals. Elevated ATGL levels in human colon cancer cells (CCC) relative to non-transformed were augmented by an obesity mediator, oleic acid (OA). In CCC and colonospheres, enriched in colon cancer stem cells (CCSC), inhibition of ATGL prevented LDs utilization and inhibited OA-stimulated growth through retinoblastoma-mediated cell cycle arrest. Further, transcriptomic analysis of CCC, with inhibited ATGL, revealed targeted pathways driving tumorigenesis, and high-fat-diet obesity facilitated tumorigenic pathways. Inhibition of ATGL in colonospheres revealed targeted pathways in human colonic tumor crypt base cells (enriched in CCSC) derived from colon cancer patients. In CCC and colonospheres, we validated selected transcripts targeted by ATGL inhibition, some with emerging roles in colonic tumorigeneses (ATG2B, PCK2, PGAM1, SPTLC2, IGFBP1, and ABCC3) and others with established roles (MYC and MUC2). These findings demonstrate obesity-promoted, ATGL-mediated colonic tumorigenesis and establish the therapeutic significance of ATGL in obesity-reinforced colon cancer progression.
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影响因子：
8.8
作者：
Ecker C;Guo L;Voicu S;Gil-de-Gómez L;Medvec A;Cortina L;Pajda J;Andolina M;Torres-Castillo M;Donato JL;Mansour S;Zynda ER;Lin PY;Varela-Rohena A;Blair IA;Riley JL
通讯作者：
Riley JL
DOI：
10.1186/s13058-018-1029-4
发表时间：
2018-09-04
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bousquenaud M;Fico F;Solinas G;Rüegg C;Santamaria-Martínez A
通讯作者：
Santamaria-Martínez A
影响因子：
9.7
作者：
DeClercq, V.;McMurray, D. N.;Chapkin, R. S.
通讯作者：
Chapkin, R. S.
DOI：
10.1016/j.bbalip.2005.08.006
发表时间：
2005-10-15
影响因子：
4.8
作者：
Hojjati, MR;Li, ZQ;Jiang, XC
通讯作者：
Jiang, XC
溶血磷脂酰胆碱酰基转移酶2介导的脂质液滴生产支持结直肠癌的化学耐药性。
影响因子：
16.6
作者：
Cotte AK;Aires V;Fredon M;Limagne E;Derangère V;Thibaudin M;Humblin E;Scagliarini A;de Barros JP;Hillon P;Ghiringhelli F;Delmas D
通讯作者：
Delmas D