Papers of note in Nature 546 (7659)

Annalisa M. VanHook

doi:10.1126/scisignal.aao1820

This week’s articles describe engineered exosomes for treating pancreatic cancer, the role of the endoplasmic reticulum in cancer cell apoptosis, the priming of brown fat for cold-induced thermogenesis, synapse loss in a mouse model of lupus, and communication between cells of different lineages during liver development.

CANCER

Targeting pancreatic cancer with exosomes

Kamerkar et al. engineered exosomes carrying an interfering RNA that targets an oncogenic form of KRAS commonly found in pancreatic cancer.

Endoplasmic reticulum calcium flux in cancer

Bononi et al. found that the tumor suppressor BRCA1-associated protein 1 (BAP1) promotes the release of Ca²⁺ from the endoplasmic reticulum and subsequent apoptosis by stabilizing an IP3 receptor.

Kuchay et al. report that inhibiting ubiquitin-dependent degradation of an IP3 receptor sensitizes PTEN-deficient tumors to photoradiation therapy by restoring the apoptosis-promoting release of Ca²⁺ from the endoplasmic reticulum.

METABOLISM

Priming the thermogenesis machinery

Emmett et al. found that histone deacetylase 3 (HDAC3) primes brown fat to generate heat in response to cold temperature.

NEUROSCIENCE

How lupus causes synapse loss

Bialas et al. report that interferons promote the loss of synapses in the brain in a mouse model of lupus by stimulating microglia to become reactive (see also McGlasson and Hunt).

DEVELOPMENTAL BIOLOGY

Interlineage communication in liver development

Using three-dimensional organoids, Camp et al. demonstrate that vascular endothelial growth factor (VEGF) signaling mediates crosstalk between different cell lineages during liver bud development.

Highlighted Articles

1. S. Kamerkar,
2. V. S. LeBleu,
3. H. Sugimoto,
4. S. Yang,
5. C. F. Ruivo,
6. S. A. Melo,
7. J. J. Lee,
8. R. Kalluri
, Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 546, 498–503 (2017).
OpenUrl
1. A. Bononi,
2. C. Giorgi,
3. S. Patergnani,
4. D. Larson,
5. K. Verbruggen,
6. M. Tanji,
7. L. Pellegrini,
8. V. Signorato,
9. F. Olivetto,
10. S. Pastorino,
11. M. Nasu,
12. A. Napolitano,
13. G. Gaudino,
14. P. Morris,
15. G. Sakamoto,
16. L. K. Ferris,
17. A. Danese,
18. A. Raimondi,
19. C. Tacchetti,
20. S. Kuchay,
21. H. I. Pass,
22. E. B. Affar,
23. H. Yang,
24. P. Pinton,
25. M. Carbone
, BAP1 regulates IP3R3-mediated Ca²⁺ flux to mitochondria suppressing cell transformation. Nature 546, 549–553 (2017).
OpenUrl
1. S. Kuchay,
2. C. Giorgi,
3. D. Simoneschi,
4. J. Pagan,
5. S. Missiroli,
6. A. Saraf,
7. L. Florens,
8. M. P. Washburn,
9. A. Collazo-Lorduy,
10. M. Castillo-Martin,
11. C. Cordon-Cardo,
12. S. M. Sebti,
13. P. Pinton,
14. M. Pagano
, PTEN counteracts FBXL2 to promote IP3R3- and Ca²⁺-mediated apoptosis limiting tumour growth. Nature 546, 554–558 (2017).
OpenUrl
1. M. J. Emmett,
2. H.-W. Lim,
3. J. Jager,
4. H. J. Richter,
5. M. Adlanmerini,
6. L. C. Peed,
7. E. R. Briggs,
8. D. J. Steger,
9. T. Ma,
10. C. A. Sims,
11. J. A. Baur,
12. L. Pei,
13. K.-J. Won,
14. P. Seale,
15. Z. Gerhart-Hines,
16. M. A. Lazar
, Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge. Nature 546, 544–548 (2017).
OpenUrl
1. A. R. Bialas,
2. J. Presumey,
3. A. Das,
4. C. E. van der Poel,
5. P. H. Lapchak,
6. L. Mesin,
7. G. Victora,
8. G. C. Tsokos,
9. C. Mawrin,
10. R. Herbst,
11. M. C. Carroll
, Microglia-dependent synapse loss in type I interferon-mediated lupus. Nature 546, 539–543 (2017).
OpenUrl
1. S. McGlasson,
2. D. Hunt
, Synapses pruned in lupus. Nature 546, 482–483 (2017).
OpenUrl
1. J. G. Camp,
2. K. Sekine,
3. T. Gerber,
4. H. Loeffler-Wirth,
5. H. Binder,
6. M. Gac,
7. S. Kanton,
8. J. Kageyama,
9. G. Damm,
10. D. Seehofer,
11. L. Belicova,
12. M. Bickle,
13. R. Barsacchi,
14. R. Okuda,
15. E. Yoshizawa,
16. M. Kimura,
17. H. Ayabe,
18. H. Taniguchi,
19. T. Takebe,
20. B. Treutlein
, Multilineage communication regulates human liver bud development from pluripotency. Nature 546, 533–538 (2017).
OpenUrl

View Abstract

[1] S. Kamerkar,
V. S. LeBleu,
H. Sugimoto,
S. Yang,
C. F. Ruivo,
S. A. Melo,
J. J. Lee,
R. Kalluri
, Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature 546, 498–503 (2017).
OpenUrl

[2] S. Kamerkar,

[3] V. S. LeBleu,

[4] H. Sugimoto,

[5] S. Yang,

[6] C. F. Ruivo,

[7] S. A. Melo,

[8] J. J. Lee,

[9] R. Kalluri

[10] A. Bononi,
C. Giorgi,
S. Patergnani,
D. Larson,
K. Verbruggen,
M. Tanji,
L. Pellegrini,
V. Signorato,
F. Olivetto,
S. Pastorino,
M. Nasu,
A. Napolitano,
G. Gaudino,
P. Morris,
G. Sakamoto,
L. K. Ferris,
A. Danese,
A. Raimondi,
C. Tacchetti,
S. Kuchay,
H. I. Pass,
E. B. Affar,
H. Yang,
P. Pinton,
M. Carbone
, BAP1 regulates IP3R3-mediated Ca²⁺ flux to mitochondria suppressing cell transformation. Nature 546, 549–553 (2017).
OpenUrl

[11] A. Bononi,

[12] C. Giorgi,

[13] S. Patergnani,

[14] D. Larson,

[15] K. Verbruggen,

[16] M. Tanji,

[17] L. Pellegrini,

[18] V. Signorato,

[19] F. Olivetto,

[20] S. Pastorino,

[21] M. Nasu,

[22] A. Napolitano,

[23] G. Gaudino,

[24] P. Morris,

[25] G. Sakamoto,

[26] L. K. Ferris,

[27] A. Danese,

[28] A. Raimondi,

[29] C. Tacchetti,

[30] S. Kuchay,

[31] H. I. Pass,

[32] E. B. Affar,

[33] H. Yang,

[34] P. Pinton,

[35] M. Carbone

[36] S. Kuchay,
C. Giorgi,
D. Simoneschi,
J. Pagan,
S. Missiroli,
A. Saraf,
L. Florens,
M. P. Washburn,
A. Collazo-Lorduy,
M. Castillo-Martin,
C. Cordon-Cardo,
S. M. Sebti,
P. Pinton,
M. Pagano
, PTEN counteracts FBXL2 to promote IP3R3- and Ca²⁺-mediated apoptosis limiting tumour growth. Nature 546, 554–558 (2017).
OpenUrl

[37] S. Kuchay,

[38] C. Giorgi,

[39] D. Simoneschi,

[40] J. Pagan,

[41] S. Missiroli,

[42] A. Saraf,

[43] L. Florens,

[44] M. P. Washburn,

[45] A. Collazo-Lorduy,

[46] M. Castillo-Martin,

[47] C. Cordon-Cardo,

[48] S. M. Sebti,

[49] P. Pinton,

[50] M. Pagano

[51] M. J. Emmett,
H.-W. Lim,
J. Jager,
H. J. Richter,
M. Adlanmerini,
L. C. Peed,
E. R. Briggs,
D. J. Steger,
T. Ma,
C. A. Sims,
J. A. Baur,
L. Pei,
K.-J. Won,
P. Seale,
Z. Gerhart-Hines,
M. A. Lazar
, Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge. Nature 546, 544–548 (2017).
OpenUrl

[52] M. J. Emmett,

[53] H.-W. Lim,

[54] J. Jager,

[55] H. J. Richter,

[56] M. Adlanmerini,

[57] L. C. Peed,

[58] E. R. Briggs,

[59] D. J. Steger,

[60] T. Ma,

[61] C. A. Sims,

[62] J. A. Baur,

[63] L. Pei,

[64] K.-J. Won,

[65] P. Seale,

[66] Z. Gerhart-Hines,

[67] M. A. Lazar

[68] A. R. Bialas,
J. Presumey,
A. Das,
C. E. van der Poel,
P. H. Lapchak,
L. Mesin,
G. Victora,
G. C. Tsokos,
C. Mawrin,
R. Herbst,
M. C. Carroll
, Microglia-dependent synapse loss in type I interferon-mediated lupus. Nature 546, 539–543 (2017).
OpenUrl

[69] A. R. Bialas,

[70] J. Presumey,

[71] A. Das,

[72] C. E. van der Poel,

[73] P. H. Lapchak,

[74] L. Mesin,

[75] G. Victora,

[76] G. C. Tsokos,

[77] C. Mawrin,

[78] R. Herbst,

[79] M. C. Carroll

[80] S. McGlasson,
D. Hunt
, Synapses pruned in lupus. Nature 546, 482–483 (2017).
OpenUrl

[81] S. McGlasson,

[82] D. Hunt

[83] J. G. Camp,
K. Sekine,
T. Gerber,
H. Loeffler-Wirth,
H. Binder,
M. Gac,
S. Kanton,
J. Kageyama,
G. Damm,
D. Seehofer,
L. Belicova,
M. Bickle,
R. Barsacchi,
R. Okuda,
E. Yoshizawa,
M. Kimura,
H. Ayabe,
H. Taniguchi,
T. Takebe,
B. Treutlein
, Multilineage communication regulates human liver bud development from pluripotency. Nature 546, 533–538 (2017).
OpenUrl

[84] J. G. Camp,

[85] K. Sekine,

[86] T. Gerber,

[87] H. Loeffler-Wirth,

[88] H. Binder,

[89] M. Gac,

[90] S. Kanton,

[91] J. Kageyama,

[92] G. Damm,

[93] D. Seehofer,

[94] L. Belicova,

[95] M. Bickle,

[96] R. Barsacchi,

[97] R. Okuda,

[98] E. Yoshizawa,

[99] M. Kimura,

[100] H. Ayabe,

[101] H. Taniguchi,

[102] T. Takebe,

[103] B. Treutlein

Papers of note in Nature 546 (7659)

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