Intravital imaging reveals how BRAF inhibition generates drug-tolerant microenvironments with high integrin β1/FAK Signaling

Cancer Cell

Volumn 27, Issue 4, 2015, Pages 574-588

  Hirata, Eishu ^a   Girotti, Maria Romina ^b   Viros, Amaya ^b   Hooper, Steven ^a   Spencer Dene, Bradley ^a   Matsuda, Michiyuki ^c   Larkin, James ^d   Marais, Richard ^b   Sahai, Erik ^a  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c KYOTO UNIVERSITY   (Japan)

^d INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

B RAF KINASE; BETA1 INTEGRIN; FIBRONECTIN; FOCAL ADHESION KINASE; MITOGEN ACTIVATED PROTEIN KINASE; MUTANT PROTEIN; N [3 (5 CHLORO 1H PYRROLO[2,3 B]PYRIDINE 3 CARBONYL) 2,4 DIFLUOROPHENYL]PROPANESULFONAMIDE; PF 562271; PROTEIN TYROSINE KINASE; INDOLE DERIVATIVE; SULFONAMIDE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOSENSOR; CELL DENSITY; CONTROLLED STUDY; DRUG EFFICACY; ENZYME INHIBITION; FEMALE; FIBROBLAST; HUMAN; HUMAN CELL; HUMAN TISSUE; MELANOMA; MELANOMA CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STROMA CELL; TREATMENT RESPONSE; TUMOR MICROENVIRONMENT; YOUNG MODULUS; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; DRUG EFFECTS; DRUG RESISTANCE; GENETICS; METABOLISM; TUMOR CELL LINE;

ANIMALS; ANTIGENS, CD29; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; FOCAL ADHESION PROTEIN-TYROSINE KINASES; HUMANS; INDOLES; MELANOMA; MICE; MICE, INBRED C57BL; PROTO-ONCOGENE PROTEINS B-RAF; SIGNAL TRANSDUCTION; SULFONAMIDES; TUMOR MICROENVIRONMENT;

EID: 84928008693     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2015.03.008     Document Type: Article

References (49)

1. Butcher D.T., Alliston T., Weaver V.M. A tense situation: forcing tumour progression. Nat. Rev. Cancer 2009, 9:108-122.
2. Calvo F., Ege N., Grande-Garcia A., Hooper S., Jenkins R.P., Chaudhry S.I., Harrington K., Williamson P., Moeendarbary E., Charras G., Sahai E. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat. Cell Biol. 2013, 15:637-646.
3. Chapman P.B., Hauschild A., Robert C., Haanen J.B., Ascierto P., Larkin J., Dummer R., Garbe C., Testori A., Maio M., et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N.Engl. J. Med. 2011, 364:2507-2516. BRIM-3 Study Group.
4. Dhomen N., Reis-Filho J.S., da Rocha Dias S., Hayward R., Savage K., Delmas V., Larue L., Pritchard C., Marais R. Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell 2009, 15:294-303.
5. Druker B.J., Talpaz M., Resta D.J., Peng B., Buchdunger E., Ford J.M., Lydon N.B., Kantarjian H., Capdeville R., Ohno-Jones S., Sawyers C.L. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N.Engl. J. Med. 2001, 344:1031-1037.
6. Druker B.J., Guilhot F., O'Brien S.G., Gathmann I., Kantarjian H., Gattermann N., Deininger M.W., Silver R.T., Goldman J.M., Stone R.M., et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N.Engl. J. Med. 2006, 355:2408-2417. IRIS Investigators.
7. 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.
8. Flaherty K.T., Puzanov I., Kim K.B., Ribas A., McArthur G.A., Sosman J.A., O'Dwyer P.J., Lee R.J., Grippo J.F., Nolop K., Chapman P.B. Inhibition of mutated, activated BRAF in metastatic melanoma. N.Engl. J. Med. 2010, 363:809-819.
9. Flaherty K.T., Infante J.R., Daud A., Gonzalez R., Kefford R.F., Sosman J., Hamid O., Schuchter L., Cebon J., Ibrahim N., et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N.Engl. J. Med 2012, 367:1694-1703.
10. Giampieri S., Manning C., Hooper S., Jones L., Hill C.S., Sahai E. Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility. Nat. Cell Biol. 2009, 11:1287-1296.
11. Gibney G.T., Zager J.S. Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies. Expert Opin. Drug Metab. Toxicol. 2013, 9:893-899.
12. Girotti M.R., Lopes F., Preece N., Niculescu-Duvaz D., Zambon A., Davies L., Whittaker S., Saturno G., Viros A., Pedersen M., et al. Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. Cancer Cell 2015, 27:85-96.
13. Harvey C.D., Ehrhardt A.G., Cellurale C., Zhong H., Yasuda R., Davis R.J., Svoboda K. A genetically encoded fluorescent sensor of ERK activity. Proc. Natl. Acad. Sci. USA 2008, 105:19264-19269.
14. Hatzivassiliou G., Song K., Yen I., Brandhuber B.J., Anderson D.J., Alvarado R., Ludlam M.J., Stokoe D., Gloor S.L., Vigers G., et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 2010, 464:431-435.
15. Heidorn S.J., Milagre C., Whittaker S., Nourry A., Niculescu-Duvas I., Dhomen N., Hussain J., Reis-Filho J.S., Springer C.J., Pritchard C., Marais R. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010, 140:209-221.
16. Huang T., Karsy M., Zhuge J., Zhong M., Liu D. B-Raf and the inhibitors: from bench to bedside. J Hematol Oncol 2013, 6:30.
17. Inukai M., Toyooka S., Ito S., Asano H., Ichihara S., Soh J., Suehisa H., Ouchida M., Aoe K., Aoe M., et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res. 2006, 66:7854-7858.
18. Janssen A., Beerling E., Medema R., van Rheenen J. Intravital FRET imaging of tumor cell viability and mitosis during chemotherapy. PLoS ONE 2013, 8:e64029.
19. Kalluri R., Zeisberg M. Fibroblasts in cancer. Nat. Rev. Cancer 2006, 6:392-401.
20. Kobayashi S., Boggon T.J., Dayaram T., Jänne P.A., Kocher O., Meyerson M., Johnson B.E., Eck M.J., Tenen D.G., Halmos B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N.Engl. J. Med. 2005, 352:786-792.
21. Komatsu N., Aoki K., Yamada M., Yukinaga H., Fujita Y., Kamioka Y., Matsuda M. Development of an optimized backbone of FRET biosensors for kinases and GTPases. Mol. Biol. Cell 2011, 22:4647-4656.
22. Larkin J., Ascierto P.A., Dréno B., Atkinson V., Liszkay G., Maio M., Mandalà M., Demidov L., Stroyakovskiy D., Thomas L., et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N.Engl. J. Med. 2014, 371:1867-1876.
23. Lito P., Pratilas C.A., Joseph E.W., Tadi M., Halilovic E., Zubrowski M., Huang A., Wong W.L., Callahan M.K., Merghoub T., et al. Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell 2012, 22:668-682.
24. Lito P., Rosen N., Solit D.B. Tumor adaptation and resistance to RAF inhibitors. Nat. Med. 2013, 19:1401-1409.
25. Maemondo M., Inoue A., Kobayashi K., Sugawara S., Oizumi S., Isobe H., Gemma A., Harada M., Yoshizawa H., Kinoshita I., et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N.Engl. J. Med. 2010, 362:2380-2388. North-East Japan Study Group.
26. Maheswaran S., Sequist L.V., Nagrath S., Ulkus L., Brannigan B., Collura C.V., Inserra E., Diederichs S., Iafrate A.J., Bell D.W., et al. Detection of mutations in EGFR in circulating lung-cancer cells. N.Engl. J. Med. 2008, 359:366-377.
27. Mok T.S., Wu Y.L., Thongprasert S., Yang C.H., Chu D.T., Saijo N., Sunpaweravong P., Han B., Margono B., Ichinose Y., et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N.Engl. J. Med. 2009, 361:947-957.
28. Muzumdar M.D., Tasic B., Miyamichi K., Li L., Luo L. A global double-fluorescent Cre reporter mouse. Genesis 2007, 45:593-605.
29. Nazarian R., Shi H., Wang Q., Kong X., Koya R.C., Lee H., Chen Z., Lee M.K., Attar N., Sazegar H., et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 2010, 468:973-977.
30. Paszek M.J., Zahir N., Johnson K.R., Lakins J.N., Rozenberg G.I., Gefen A., Reinhart-King C.A., Margulies S.S., Dembo M., Boettiger D., et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 2005, 8:241-254.
31. Pedersen M., Kusters-Vandevelde H.V., Viros A., Groenen P.J., Sanchez-Laorden B., Gilhuis J.H., van Engen-van Grunsven I.A., Renier W., Schieving J., Niculescu-Duvaz I., et al. Primary melanoma of the CNS in children is driven by congenital expression of oncogenic NRAS in melanocytes. Cancer Discov 2013, 3:458-469.
32. Pietras K., Pahler J., Bergers G., Hanahan D. Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Med. 2008, 5:e19.
33. Poulikakos P.I., Rosen N. Mutant BRAF melanomas-dependence and resistance. Cancer Cell 2011, 19:11-15.
34. Poulikakos P.I., Zhang C., Bollag G., Shokat K.M., Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature 2010, 464:427-430.
35. Poulikakos P.I., Persaud Y., Janakiraman M., Kong X., Ng C., Moriceau G., Shi H., Atefi M., Titz B., Gabay M.T., et al. RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature 2011, 480:387-390.
36. Rosell R., Molina M.A., Costa C., Simonetti S., Gimenez-Capitan A., Bertran-Alamillo J., Mayo C., Moran T., Mendez P., Cardenal F., et al. Pretreatment EGFR T790M mutation and BRCA1 mRNA expression in erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations. Clin. Cancer Res. 2011, 17:1160-1168.
37. Shawver L.K., Slamon D., Ullrich A. Smart drugs: tyrosine kinase inhibitors in cancer therapy. Cancer Cell 2002, 1:117-123.
38. Shi H., Hugo W., Kong X., Hong A., Koya R.C., Moriceau G., Chodon T., Guo R., Johnson D.B., Dahlman K.B., et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov 2014, 4:80-93.
39. Sordella R., Bell D.W., Haber D.A., Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004, 305:1163-1167.
40. Sosman J.A., Kim K.B., Schuchter L., Gonzalez R., Pavlick A.C., Weber J.S., McArthur G.A., Hutson T.E., Moschos S.J., Flaherty K.T., et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N.Engl. J. Med. 2012, 366:707-714.
41. Straussman R., Morikawa T., Shee K., Barzily-Rokni M., Qian Z.R., Du J., Davis A., Mongare M.M., Gould J., Frederick D.T., et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 2012, 487:500-504.
42. Sulzmaier F.J., Jean C., Schlaepfer D.D. FAK in cancer: mechanistic findings and clinical applications. Nat. Rev. Cancer 2014, 14:598-610.
43. Turke A.B., Zejnullahu K., Wu Y.L., Song Y., Dias-Santagata D., Lifshits E., Toschi L., Rogers A., Mok T., Sequist L., et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 2010, 17:77-88.
44. Van Allen E.M., Wagle N., Sucker A., Treacy D.J., Johannessen C.M., Goetz E.M., Place C.S., Taylor-Weiner A., Whittaker S., Kryukov G.V., et al. The genetic landscape of clinical resistance to RAF inhibition in metastatic melanoma. Cancer Discov 2014, 4:94-109. Dermatologic Cooperative Oncology Group of Germany (DeCOG).
45. Villanueva J., Vultur A., Lee J.T., Somasundaram R., Fukunaga-Kalabis M., Cipolla A.K., Wubbenhorst B., Xu X., Gimotty P.A., Kee D., et al. Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell 2010, 18:683-695.
46. Villanueva J., Vultur A., Herlyn M. Resistance to BRAF inhibitors: unraveling mechanisms and future treatment options. Cancer Res. 2011, 71:7137-7140.
47. Wagle N., Van Allen E.M., Treacy D.J., Frederick D.T., Cooper Z.A., Taylor-Weiner A., Rosenberg M., Goetz E.M., Sullivan R.J., Farlow D.N., et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov 2014, 4:61-68.
48. Watson I.R., Li L., Cabeceiras P.K., Mahdavi M., Gutschner T., Genovese G., Wang G., Fang Z., Tepper J.M., Stemke-Hale K., et al. The RAC1 P29S hotspot mutation in melanoma confers resistance to pharmacological inhibition of RAF. Cancer Res. 2014, 74:4845-4852.
49. Wilson T.R., Fridlyand J., Yan Y., Penuel E., Burton L., Chan E., Peng J., Lin E., Wang Y., Sosman J., et al. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 2012, 487:505-509.