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ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.

Linares JF, Cordes T, Duran A, Reina-Campos M, Valencia T, Ahn CS, Castilla EA, Moscat J, Metallo CM, Diaz-Meco MT.

Cell Metab. 2017 Dec 5;26(6):817-829.e6. doi: 10.1016/j.cmet.2017.09.001. Epub 2017 Oct 5.


Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis.

Valencia T, Kim JY, Abu-Baker S, Moscat-Pardos J, Ahn CS, Reina-Campos M, Duran A, Castilla EA, Metallo CM, Diaz-Meco MT, Moscat J.

Cancer Cell. 2014 Jul 14;26(1):121-135. doi: 10.1016/j.ccr.2014.05.004. Epub 2014 Jul 4.


Unique metabolic features of pancreatic cancer stroma: relevance to the tumor compartment, prognosis, and invasive potential.

Knudsen ES, Balaji U, Freinkman E, McCue P, Witkiewicz AK.

Oncotarget. 2016 Nov 29;7(48):78396-78411. doi: 10.18632/oncotarget.11893.


Targeting Stromal Glutamine Synthetase in Tumors Disrupts Tumor Microenvironment-Regulated Cancer Cell Growth.

Yang L, Achreja A, Yeung TL, Mangala LS, Jiang D, Han C, Baddour J, Marini JC, Ni J, Nakahara R, Wahlig S, Chiba L, Kim SH, Morse J, Pradeep S, Nagaraja AS, Haemmerle M, Kyunghee N, Derichsweiler M, Plackemeier T, Mercado-Uribe I, Lopez-Berestein G, Moss T, Ram PT, Liu J, Lu X, Mok SC, Sood AK, Nagrath D.

Cell Metab. 2016 Nov 8;24(5):685-700. doi: 10.1016/j.cmet.2016.10.011.


Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment.

Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, Wang C, Pavlides S, Martinez-Cantarin MP, Capozza F, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Caro J, Lisanti MP, Sotgia F.

Cell Cycle. 2010 Sep 1;9(17):3515-33. Epub 2010 Sep 9.


Glucose deprivation induces chemoresistance in colorectal cancer cells by increasing ATF4 expression.

Hu YL, Yin Y, Liu HY, Feng YY, Bian ZH, Zhou LY, Zhang JW, Fei BJ, Wang YG, Huang ZH.

World J Gastroenterol. 2016 Jul 21;22(27):6235-45. doi: 10.3748/wjg.v22.i27.6235.


Tumor-stroma metabolic relationship based on lactate shuttle can sustain prostate cancer progression.

Sanità P, Capulli M, Teti A, Galatioto GP, Vicentini C, Chiarugi P, Bologna M, Angelucci A.

BMC Cancer. 2014 Mar 5;14:154. doi: 10.1186/1471-2407-14-154.


Glutamine fuels a vicious cycle of autophagy in the tumor stroma and oxidative mitochondrial metabolism in epithelial cancer cells: implications for preventing chemotherapy resistance.

Ko YH, Lin Z, Flomenberg N, Pestell RG, Howell A, Sotgia F, Lisanti MP, Martinez-Outschoorn UE.

Cancer Biol Ther. 2011 Dec 15;12(12):1085-97. doi: 10.4161/cbt.12.12.18671. Epub 2011 Dec 15.


Multiple pathways are involved in the anoxia response of SKIP3 including HuR-regulated RNA stability, NF-kappaB and ATF4.

Rzymski T, Paantjens A, Bod J, Harris AL.

Oncogene. 2008 Jul 31;27(33):4532-43. doi: 10.1038/onc.2008.100. Epub 2008 Apr 14.


TRIB3 enhances cell viability during glucose deprivation in HEK293-derived cells by upregulating IGFBP2, a novel nutrient deficiency survival factor.

Örd T, Örd D, Adler P, Vilo J, Örd T.

Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2492-505. doi: 10.1016/j.bbamcr.2015.06.006. Epub 2015 Jun 18.


Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment.

Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Tanowitz HB, Sotgia F, Lisanti MP.

Int J Biochem Cell Biol. 2011 Jul;43(7):1045-51. doi: 10.1016/j.biocel.2011.01.023. Epub 2011 Feb 15. Review.


An aryl hydrocarbon receptor induces VEGF expression through ATF4 under glucose deprivation in HepG2.

Terashima J, Tachikawa C, Kudo K, Habano W, Ozawa S.

BMC Mol Biol. 2013 Dec 12;14:27. doi: 10.1186/1471-2199-14-27.


Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion.

Zhang J, Fan J, Venneti S, Cross JR, Takagi T, Bhinder B, Djaballah H, Kanai M, Cheng EH, Judkins AR, Pawel B, Baggs J, Cherry S, Rabinowitz JD, Thompson CB.

Mol Cell. 2014 Oct 23;56(2):205-218. doi: 10.1016/j.molcel.2014.08.018. Epub 2014 Sep 18.


ATF4 Targets RET for Degradation and Is a Candidate Tumor Suppressor Gene in Medullary Thyroid Cancer.

Bagheri-Yarmand R, Williams MD, Grubbs EG, Gagel RF.

J Clin Endocrinol Metab. 2017 Mar 1;102(3):933-941. doi: 10.1210/jc.2016-2878.


Crosstalk between ATF4 and MTA1/HDAC1 promotes osteosarcoma progression.

Zeng H, Zhang JM, Du Y, Wang J, Ren Y, Li M, Li H, Cai Z, Chu Q, Yang C.

Oncotarget. 2016 Feb 9;7(6):7329-42. doi: 10.18632/oncotarget.6940.


Tumor suppressor BTG1 promotes PRMT1-mediated ATF4 function in response to cellular stress.

Yuniati L, van der Meer LT, Tijchon E, van Ingen Schenau D, van Emst L, Levers M, Palit SA, Rodenbach C, Poelmans G, Hoogerbrugge PM, Shan J, Kilberg MS, Scheijen B, van Leeuwen FN.

Oncotarget. 2016 Jan 19;7(3):3128-43. doi: 10.18632/oncotarget.6519.


Pyruvate kinase expression (PKM1 and PKM2) in cancer-associated fibroblasts drives stromal nutrient production and tumor growth.

Chiavarina B, Whitaker-Menezes D, Martinez-Outschoorn UE, Witkiewicz AK, Birbe R, Howell A, Pestell RG, Smith J, Daniel R, Sotgia F, Lisanti MP.

Cancer Biol Ther. 2011 Dec 15;12(12):1101-13. doi: 10.4161/cbt.12.12.18703. Epub 2011 Dec 15.


Oncogenes and inflammation rewire host energy metabolism in the tumor microenvironment: RAS and NFκB target stromal MCT4.

Martinez-Outschoorn UE, Curry JM, Ko YH, Lin Z, Tuluc M, Cognetti D, Birbe RC, Pribitkin E, Bombonati A, Pestell RG, Howell A, Sotgia F, Lisanti MP.

Cell Cycle. 2013 Aug 15;12(16):2580-97. doi: 10.4161/cc.25510. Epub 2013 Jul 8.


The reactive stroma microenvironment and prostate cancer progression.

Barron DA, Rowley DR.

Endocr Relat Cancer. 2012 Oct 30;19(6):R187-204. doi: 10.1530/ERC-12-0085. Print 2012 Dec. Review.


GRP78 inhibition enhances ATF4-induced cell death by the deubiquitination and stabilization of CHOP in human osteosarcoma.

Luo J, Xia Y, Luo J, Li J, Zhang C, Zhang H, Ma T, Yang L, Kong L.

Cancer Lett. 2017 Dec 1;410:112-123. doi: 10.1016/j.canlet.2017.09.021. Epub 2017 Sep 22.


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