Metabolic Reprogramming of Stromal Fibroblasts through p62-mTORC1 Signaling Promotes Inflammation and Tumorigenesis

Cancer Cell

Volumn 26, Issue 1, 2014, Pages 121-135

  Valencia, Tania ^a   Kim, JiYoung ^a   Abu Baker, Shadi ^b   Moscat Pardos, Jorge ^a   Ahn, ChristopherS ^c   Reina Campos, Miguel ^a   Duran, Angeles ^a   Castilla, EliasA ^b   Metallo, ChristianM ^c,d   Diaz Meco, MariaT ^a   Moscat, Jorge ^a  

^a BURNHAM INSTITUTE   (United States)

^b UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^d UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 6; MYC PROTEIN; PROTEIN P62; REACTIVE OXYGEN METABOLITE; TRANSFORMING GROWTH FACTOR BETA;

AGING; AMINO ACID METABOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARCINOGENESIS; CYTOKINE PRODUCTION; FIBROBLAST; GLUCOSE METABOLISM; INFLAMMATION; INTRACELLULAR SIGNALING; MALE; METABOLIC REGULATION; MOUSE; NONHUMAN; OXIDATION REDUCTION REACTION; PHENOTYPE; PRIORITY JOURNAL; PROSTATE CANCER CELL LINE; PROSTATE EPITHELIUM; PROSTATE HYPERTROPHY; PROSTATIC INTRAEPITHELIAL NEOPLASIA; REGULATORY MECHANISM; STROMA; TUMOR MICROENVIRONMENT; TUMOR PROMOTION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; AMINO ACIDS; ANIMALS; CELL COMMUNICATION; CELL LINE, TUMOR; CELL TRANSFORMATION, NEOPLASTIC; COCULTURE TECHNIQUES; ENERGY METABOLISM; FIBROBLASTS; GLUCOSE; HEAT-SHOCK PROTEINS; HEK293 CELLS; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; INTERLEUKIN-6; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MULTIPROTEIN COMPLEXES; NEOPLASM INVASIVENESS; OXIDATIVE STRESS; PROSTATIC HYPERPLASIA; PROSTATIC INTRAEPITHELIAL NEOPLASIA; PROSTATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-MYC; PTEN PHOSPHOHYDROLASE; RNA INTERFERENCE; SIGNAL TRANSDUCTION; STROMAL CELLS; TIME FACTORS; TOR SERINE-THREONINE KINASES; TRANSFECTION; TUMOR MICROENVIRONMENT;

EID: 84906906535     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2014.05.004     Document Type: Article

References (62)

1. Ammirante M., Luo J.L., Grivennikov S., Nedospasov S., Karin M. B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 2010, 464:302-305.
2. Azevedo A., Cunha V., Teixeira A.L., Medeiros R. IL-6/IL-6R as a potential key signaling pathway in prostate cancer development. World J. Clin. Oncol. 2011, 2:384-396.
3. Bannai S., Tateishi N. Role of membrane transport in metabolism and function of glutathione in mammals. J.Membr. Biol. 1986, 89:1-8.
4. Barron D.A., Rowley D.R. The reactive stroma microenvironment and prostate cancer progression. Endocr. Relat. Cancer 2012, 19:R187-R204.
5. Bissell M.J., Radisky D. Putting tumours in context. Nat. Rev. Cancer 2001, 1:46-54.
6. Calon A., Espinet E., Palomo-Ponce S., Tauriello D.V., Iglesias M., Céspedes M.V., Sevillano M., Nadal C., Jung P., Zhang X.H., et al. Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell 2012, 22:571-584.
7. Coussens L.M., Werb Z. Inflammation and cancer. Nature 2002, 420:860-867.
8. Dang C.V. MYC on the path to cancer. Cell 2012, 149:22-35.
9. De Marzo A.M., Platz E.A., Sutcliffe S., Xu J., Grönberg H., Drake C.G., Nakai Y., Isaacs W.B., Nelson W.G. Inflammation in prostate carcinogenesis. Nat. Rev. Cancer 2007, 7:256-269.
10. DeBerardinis R.J., Thompson C.B. Cellular metabolism and disease: what do metabolic outliers teach us?. Cell 2012, 148:1132-1144.
11. Di Cristofano A., Pesce B., Cordon-Cardo C., Pandolfi P.P. Pten is essential for embryonic development and tumour suppression. Nat. Genet. 1998, 19:348-355.
12. Diaz-Meco M.T., Moscat J. The atypical PKCs in inflammation: NF-κB and beyond. Immunol. Rev. 2012, 246:154-167.
13. Durán A., Serrano M., Leitges M., Flores J.M., Picard S., Brown J.P., Moscat J., Diaz-Meco M.T. The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis. Dev. Cell 2004, 6:303-309.
14. Duran A., Linares J.F., Galvez A.S., Wikenheiser K., Flores J.M., Diaz-Meco M.T., Moscat J. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 2008, 13:343-354.
15. Duran A., Amanchy R., Linares J.F., Joshi J., Abu-Baker S., Porollo A., Hansen M., Moscat J., Diaz-Meco M.T. p62 is a key regulator of nutrient sensing in the mTORC1 pathway. Mol. Cell 2011, 44:134-146.
16. Erez N., Truitt M., Olson P., Arron S.T., Hanahan D. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell 2010, 17:135-147.
17. Franco O.E., Hayward S.W. Targeting the tumor stroma as a novel therapeutic approach for prostate cancer. Adv. Pharmacol. 2012, 65:267-313.
18. Gaggioli C., Hooper S., Hidalgo-Carcedo C., Grosse R., Marshall J.F., Harrington K., Sahai E. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat. Cell Biol. 2007, 9:1392-1400.
19. Galavotti S., Bartesaghi S., Faccenda D., Shaked-Rabi M., Sanzone S., McEvoy A., Dinsdale D., Condorelli F., Brandner S., Campanella M., et al. The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells. Oncogene 2013, 32:699-712.
20. Gout P.W., Kang Y.J., Buckley D.J., Bruchovsky N., Buckley A.R. Increased cystine uptake capability associated with malignant progression of Nb2 lymphoma cells. Leukemia 1997, 11:1329-1337.
21. Greenberg N.M., DeMayo F., Finegold M.J., Medina D., Tilley W.D., Aspinall J.O., Cunha G.R., Donjacour A.A., Matusik R.J., Rosen J.M. Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA 1995, 92:3439-3443.
22. Grivennikov S.I., Greten F.R., Karin M. Immunity, inflammation, and cancer. Cell 2010, 140:883-899.
23. Guo Y., Xu F., Lu T., Duan Z., Zhang Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat. Rev. 2012, 38:904-910.
24. Guo J.Y., Xia B., White E. Autophagy-mediated tumor promotion. Cell 2013, 155:1216-1219.
25. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
26. Hanahan D., Coussens L.M. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 2012, 21:309-322.
27. Inami Y., Waguri S., Sakamoto A., Kouno T., Nakada K., Hino O., Watanabe S., Ando J., Iwadate M., Yamamoto M., et al. Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells. J.Cell Biol. 2011, 193:275-284.
28. Inman G.J., Nicolás F.J., Callahan J.F., Harling J.D., Gaster L.M., Reith A.D., Laping N.J., Hill C.S. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Mol. Pharmacol. 2002, 62:65-74.
29. Inoue D., Suzuki T., Mitsuishi Y., Miki Y., Suzuki S., Sugawara S., Watanabe M., Sakurada A., Endo C., Uruno A., et al. Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma. Cancer Sci. 2012, 103:760-766.
30. Johansson M., Denardo D.G., Coussens L.M. Polarized immune responses differentially regulate cancer development. Immunol. Rev. 2008, 222:145-154.
31. Kim J.Y., Valencia T., Abu-Baker S., Linares J., Lee S.J., Yajima T., Chen J., Eroshkin A., Castilla E.A., Brill L.M., et al. c-Myc phosphorylation by PKCζ represses prostate tumorigenesis. Proc. Natl. Acad. Sci. U S A 2013, 110:6418-6423.
32. Kojima Y., Acar A., Eaton E.N., Mellody K.T., Scheel C., Ben-Porath I., Onder T.T., Wang Z.C., Richardson A.L., Weinberg R.A., Orimo A. Autocrine TGF-beta and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc. Natl. Acad. Sci. U S A 2010, 107:20009-20014.
33. Komatsu M., Kurokawa H., Waguri S., Taguchi K., Kobayashi A., Ichimura Y., Sou Y.S., Ueno I., Sakamoto A., Tong K.I., et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat. Cell Biol. 2010, 12:213-223.
34. Levine B., Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008, 132:27-42.
35. Li L., Shen C., Nakamura E., Ando K., Signoretti S., Beroukhim R., Cowley G.S., Lizotte P., Liberzon E., Bair S., et al. SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer. Cancer Cell 2013, 24:738-750.
36. Ling J., Kang Y., Zhao R., Xia Q., Lee D.F., Chang Z., Li J., Peng B., Fleming J.B., Wang H., et al. KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma. Cancer Cell 2012, 21:105-120.
37. Lisanti M.P., Martinez-Outschoorn U.E., Sotgia F. Oncogenes induce the cancer-associated fibroblast phenotype: metabolic symbiosis and "fibroblast addiction" are new therapeutic targets for drug discovery. Cell Cycle 2013, 12:2723-2732.
38. Locasale J.W. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer 2013, 13:572-583.
39. Ma L., Tao Y., Duran A., Llado V., Galvez A., Barger J.F., Castilla E.A., Chen J., Yajima T., Porollo A., et al. Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis. Cell 2013, 152:599-611.
40. Metallo C.M., Vander Heiden M.G. Understanding metabolic regulation and its influence on cell physiology. Mol. Cell 2013, 49:388-398.
41. Moscat J., Diaz-Meco M.T. p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 2009, 137:1001-1004.
42. Moscat J., Diaz-Meco M.T. Feedback on fat: p62-mTORC1-autophagy connections. Cell 2011, 147:724-727.
43. Moscat J., Diaz-Meco M.T. p62: a versatile multitasker takes oncancer. Trends Biochem. Sci. 2012, 37:230-236.
44. Moscat J., Diaz-Meco M.T., Wooten M.W. Signal integration anddiversification through the p62 scaffold protein. Trends Biochem. Sci. 2007, 32:95-100.
45. Nyström M.L., Thomas G.J., Stone M., Mackenzie I.C., Hart I.R., Marshall J.F. Development of a quantitative method to analyse tumour cell invasion in organotypic culture. J.Pathol. 2005, 205:468-475.
46. Olson M.V., Lee J., Zhang F., Wang A., Dong Z. Inducible nitric oxide synthase activity is essential for inhibition of prostatic tumor growth byinterferon-beta gene therapy. Cancer Gene Ther. 2006, 13:676-685.
47. Ostman A., Augsten M. Cancer-associated fibroblasts and tumorgrowth-bystanders turning into key players. Curr. Opin. Genet. Dev. 2009, 19:67-73.
48. Peña-Llopis S., Vega-Rubin-de-Celis S., Schwartz J.C., Wolff N.C., Tran T.A., Zou L., Xie X.J., Corey D.R., Brugarolas J. Regulation of TFEB and V-ATPases by mTORC1. EMBO J. 2011, 30:3242-3258.
49. Possemato R., Marks K.M., Shaul Y.D., Pacold M.E., Kim D., Birsoy K., Sethumadhavan S., Woo H.K., Jang H.G., Jha A.K., et al. Functional genomics reveal that the serine synthesis pathway is essential inbreast cancer. Nature 2011, 476:346-350.
50. Ridky T.W., Chow J.M., Wong D.J., Khavari P.A. Invasive three-dimensional organotypic neoplasia from multiple normal human epithelia. Nat. Med. 2010, 16:1450-1455.
51. Rolland P., Madjd Z., Durrant L., Ellis I.O., Layfield R., Spendlove I. The ubiquitin-binding protein p62 is expressed in breast cancers showing features of aggressive disease. Endocr. Relat. Cancer 2007, 14:73-80.
52. Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T. Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62. Mol. Cell. Biol. 1998, 18:3069-3080.
53. Santos A.M., Jung J., Aziz N., Kissil J.L., Puré E. Targeting fibroblast activation protein inhibits tumor stromagenesis and growth in mice. J.Clin. Invest. 2009, 119:3613-3625.
54. Schafer Z.T., Brugge J.S. IL-6 involvement in epithelial cancers. J.Clin. Invest. 2007, 117:3660-3663.
55. Schäfer M., Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat. Rev. Mol. Cell Biol. 2008, 9:628-638.
56. Schauer I.G., Ressler S.J., Tuxhorn J.A., Dang T.D., Rowley D.R. Elevated epithelial expression of interleukin-8 correlates with myofibroblast reactive stroma in benign prostatic hyperplasia. Urology 2008, 72:205-213.
57. Shen M.M., Abate-Shen C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 2010, 24:1967-2000.
58. Thompson H.G., Harris J.W., Wold B.J., Lin F., Brody J.P. p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells. Oncogene 2003, 22:2322-2333.
59. Trimboli A.J., Cantemir-Stone C.Z., Li F., Wallace J.A., Merchant A., Creasap N., Thompson J.C., Caserta E., Wang H., Chong J.L., et al. Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature 2009, 461:1084-1091.
60. Vander Heiden M.G. Exploiting tumor metabolism: challenges for clinical translation. J.Clin. Invest. 2013, 123:3648-3651.
61. Vander Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324:1029-1033.
62. Vander Heiden M.G., Locasale J.W., Swanson K.D., Sharfi H., Heffron G.J., Amador-Noguez D., Christofk H.R., Wagner G., Rabinowitz J.D., Asara J.M., Cantley L.C. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 2010, 329:1492-1499.