CoChat
Sign Up
Cited by 366

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents

Degtyarev, Michael, De Mazière, Ann, Orr, Christine, Lin, Jie, Lee, Brian B., Tien, Janet Y., Prior, Wei W., van Dijk, Suzanne, Wu, Hong, Gray, Daniel C., Davis, David P., Stern, Howard M., Murray, Lesley J., Hoeflich, Klaus P., Klumperman, Judith, Friedman, Lori S., Lin, Kui·2008·The Journal of Cell Biology
DOI 10.1083/jcb.200801099PMC PMC2557046
Open this paper in CoChat — free account

Abstract

Although Akt is known as a survival kinase, inhibitors of the phosphatidylinositol 3-kinase (PI3K)–Akt pathway do not always induce substantial apoptosis. We show that silencing Akt1 alone, or any combination of Akt isoforms, can suppress the growth of tumors established from phosphatase and tensin homologue–null human cancer cells. Although these findings indicate that Akt is essential for tumor maintenance, most tumors eventually rebound. Akt knockdown or inactivation with small molecule inhibitors did not induce significant apoptosis but rather markedly increased autophagy. Further treatment with the lysosomotropic agent chloroquine caused accumulation of abnormal autophagolysosomes and reactive oxygen species, leading to accelerated cell death in vitro and complete tumor remission in vivo. Cell death was also promoted when Akt inhibition was combined with the vacuolar H+–adenosine triphosphatase inhibitor bafilomycin A1 or with cathepsin inhibition. These results suggest that blocking lysosomal degradation can be detrimental to cancer cell survival when autophagy is activated, providing rationale for a new therapeutic approach to enhancing the anticancer efficacy of PI3K–Akt pathway inhibition.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1083/jcb.200801099

Cites

5 of 5 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 5 references

Research works printed but not linked: 66

  1. 2005, Oncogene., 24, 7455, 10.1038/sj.onc.1209085 · DOI
  2. 2005, J. Clin. Invest., 115, 2618, 10.1172/JCI26273 · DOI
  3. 2007, J. Clin. Invest., 117, 326, 10.1172/JCI28833 · DOI
  4. 2001, J. Biol. Chem., 276, 35243, 10.1074/jbc.C100319200 · DOI
  5. 2005, Biochem. J., 385, 399, 10.1042/BJ20041140 · DOI
  6. 2005, Mol. Cell. Biol., 25, 1025, 10.1128/MCB.25.3.1025-1040.2005 · DOI
  7. 2001, Cell Death Differ., 8, 569, 10.1038/sj.cdd.4400852 · DOI
  8. 2007, Blood., 110, 313
  9. 2006, Genes Dev., 20, 1569, 10.1101/gad.1395006 · DOI
  10. 2001, Genes Dev., 15, 2203, 10.1101/gad.913901 · DOI
  11. 2001, Science., 292, 1728, 10.1126/science.292.5522.1728 · DOI
  12. 2001, J. Biol. Chem., 276, 38349, 10.1074/jbc.C100462200 · DOI
  13. 1986, Cell Tissue Res., 243, 641, 10.1007/BF00218073 · DOI
  14. 2006, Cancer Cell., 10, 51, 10.1016/j.ccr.2006.06.001 · DOI
  15. 1998, Curr. Opin. Cell Biol., 10, 262, 10.1016/S0955-0674(98)80149-X · DOI
  16. 2004, J. Biol. Chem., 279, 44113, 10.1074/jbc.M405323200 · DOI
  17. 2005, Mol. Cell. Biol., 25, 1869, 10.1128/MCB.25.5.1869-1878.2005 · DOI
  18. 2006, Cancer Cell., 9, 341, 10.1016/j.ccr.2006.03.029 · DOI
  19. 2001, J. Cell Biol., 153, 999, 10.1083/jcb.153.5.999 · DOI
  20. 2007, Int. J. Oncol., 31, 753
  21. 2006, Mol. Cancer Ther., 5, 713, 10.1158/1535-7163.MCT-05-0484 · DOI
  22. 2005, J. Cell Sci., 118, 3091, 10.1242/jcs.02447 · DOI
  23. 2005, Cancer Res., 65, 9751, 10.1158/0008-5472.CAN-04-4531 · DOI
  24. 2007, BMC Biotechnol., 7, 61, 10.1186/1472-6750-7-61 · DOI
  25. 2007, Cancer Res., 67, 2217, 10.1158/0008-5472.CAN-06-3520 · DOI
  26. 2002, Cancer Res., 62, 6141
  27. 2006, Cancer Res., 66, 999, 10.1158/0008-5472.CAN-05-2720 · DOI
  28. 2005, J. Cell Biol., 171, 1023, 10.1083/jcb.200505087 · DOI
  29. 2007, Proc. Natl. Acad. Sci. USA., 104, 7438, 10.1073/pnas.0605874104 · DOI
  30. 2004, Cell Death Differ., 11, 448, 10.1038/sj.cdd.4401359 · DOI
  31. 2001, FASEB J., 15, 1953, 10.1096/fj.01-0198com · DOI
  32. 2008, Autophagy., 4, 151, 10.4161/auto.5338 · DOI · Paper page
  33. 2006, Cell., 125, 733, 10.1016/j.cell.2006.03.035 · DOI · Paper page
  34. 2005, Nat. Rev. Cancer., 5, 886, 10.1038/nrc1738 · DOI
  35. 2005, J. Clin. Invest., 115, 2679, 10.1172/JCI26390 · DOI
  36. 1997, Science., 275, 1943, 10.1126/science.275.5308.1943 · DOI · Paper page
  37. 2006, Cancer Lett., 237, 167, 10.1016/j.canlet.2005.06.007 · DOI
  38. 2006, J. Biol. Chem., 281, 31380, 10.1016/S0021-9258(19)84050-4 · DOI
  39. 2004, Int. J. Biochem. Cell Biol., 36, 2405, 10.1016/j.biocel.2004.04.011 · DOI
  40. 2005, Cell., 120, 237, 10.1016/j.cell.2004.11.046 · DOI · Paper page
  41. 2007, Cancer Res., 67, 167, 10.1158/0008-5472.CAN-06-3782 · DOI
  42. 2008, Cancer Res., 68, 580, 10.1158/0008-5472.CAN-07-3091 · DOI
  43. 2006, Mar. Environ. Res., 62, S420, 10.1016/j.marenvres.2006.04.055 · DOI
  44. 1998, J. Pathol., 185, 324, 10.1002/(SICI)1096-9896(199807)185:3<324::AID-PATH72>3.0.CO;2-9 · DOI
  45. 2005, Cancer Res., 65, 8975, 10.1158/0008-5472.CAN-05-0269 · DOI
  46. 2008, Cell. Signal., 1, 21
  47. 2003, Genes Dev., 17, 1352, 10.1101/gad.1089403 · DOI
  48. 2000, J. Biol. Chem., 275, 992, 10.1074/jbc.275.2.992 · DOI
  49. 2006, Curr. Opin. Oncol., 18, 77, 10.1097/01.cco.0000198021.99347.b9 · DOI
  50. 2006, Mol. Cell., 22, 159, 10.1016/j.molcel.2006.03.029 · DOI · Paper page
  51. 2006, Neurobiol. Aging., 27, 576, 10.1016/j.neurobiolaging.2005.12.006 · DOI · Paper page
  52. 1982, Proc. Natl. Acad. Sci. USA., 79, 1889, 10.1073/pnas.79.6.1889 · DOI
  53. 1979, J. Natl. Cancer Inst., 62, 1575
  54. 2006, Cancer Cell., 10, 269, 10.1016/j.ccr.2006.08.022 · DOI
  55. 2004, Cancer Res., 64, 7002, 10.1158/0008-5472.CAN-04-1399 · DOI
  56. 2006, Trends Cell Biol., 16, 461, 10.1016/j.tcb.2006.07.001 · DOI
  57. 1999, Proc. Natl. Acad. Sci. USA., 96, 6199, 10.1073/pnas.96.11.6199 · DOI
  58. 2005, Cancer Res., 65, 3336, 10.1158/0008-5472.CAN-04-3640 · DOI
  59. 2001, Cancer Res., 61, 589
  60. 2006, Chem. Biol. Interact., 163, 29, 10.1016/j.cbi.2006.04.013 · DOI
  61. 2005, Development., 132, 2943, 10.1242/dev.01864 · DOI
  62. 2005, Mol. Cell. Biol., 25, 10407, 10.1128/MCB.25.23.10407-10418.2005 · DOI
  63. 2005, Mol. Cell., 20, 539, 10.1016/j.molcel.2005.10.033 · DOI
  64. 2006, Nat. Cell Biol., 8, 1124, 10.1038/ncb1482 · DOI · Paper page
  65. 2006, Proc. Natl. Acad. Sci. USA., 103, 4952, 10.1073/pnas.0511288103 · DOI
  66. 2008, Autophagy., 4, 378, 10.4161/auto.5633 · DOI

Cited by

Sorted by citations

See all 366

Metadata

Authors
Degtyarev, M., De Mazière, A., Orr, C., Lin, J., Lee, B. B., Tien, J. Y., Prior, W. W., van Dijk, S., Wu, H., Gray, D. C., Davis, D. P., Stern, H. M., Murray, L. J., Hoeflich, K. P., Klumperman, J., Friedman, L. S., & Lin, K.
Affiliations
  • 1Genentech, Inc., South San Francisco, CA 94080
  • 2Cell Microscopy Center, Department of Cell Biology and Institute for Biomembranes, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands
  • 3Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2008-10-06
Volume
183
Issue
1
Pages
101-116
ISSN
  • 1540-8140
  • 0021-9525
DOI
10.1083/jcb.200801099
PMC
PMC2557046
Cited by
366
References
5
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review