Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis. / Tran, Phuoc T; Shroff, Emelyn H; Burns, Timothy F; Thiyagarajan, Saravanan; Das, Sandhya T; Zabuawala, Tahera; Chen, Joy; Cho, Yoon-Jae; Luong, Richard; Tamayo, Pablo; Salih, Tarek; Aziz, Khaled; Adam, Stacey J; Vicent, Silvestre; Nielsen, Carsten Haagen; Withofs, Nadia; Sweet-Cordero, Alejandro; Gambhir, Sanjiv S; Rudin, Charles M; Felsher, Dean W.

In: P L o S Genetics (Online), Vol. 8, No. 5, 24.05.2012, p. 1-10.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Tran, PT, Shroff, EH, Burns, TF, Thiyagarajan, S, Das, ST, Zabuawala, T, Chen, J, Cho, Y-J, Luong, R, Tamayo, P, Salih, T, Aziz, K, Adam, SJ, Vicent, S, Nielsen, CH, Withofs, N, Sweet-Cordero, A, Gambhir, SS, Rudin, CM & Felsher, DW 2012, 'Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis', P L o S Genetics (Online), vol. 8, no. 5, pp. 1-10. https://doi.org/10.1371/journal.pgen.1002650

APA

Tran, P. T., Shroff, E. H., Burns, T. F., Thiyagarajan, S., Das, S. T., Zabuawala, T., Chen, J., Cho, Y-J., Luong, R., Tamayo, P., Salih, T., Aziz, K., Adam, S. J., Vicent, S., Nielsen, C. H., Withofs, N., Sweet-Cordero, A., Gambhir, S. S., Rudin, C. M., & Felsher, D. W. (2012). Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis. P L o S Genetics (Online), 8(5), 1-10. https://doi.org/10.1371/journal.pgen.1002650

Vancouver

Tran PT, Shroff EH, Burns TF, Thiyagarajan S, Das ST, Zabuawala T et al. Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis. P L o S Genetics (Online). 2012 May 24;8(5):1-10. https://doi.org/10.1371/journal.pgen.1002650

Author

Tran, Phuoc T ; Shroff, Emelyn H ; Burns, Timothy F ; Thiyagarajan, Saravanan ; Das, Sandhya T ; Zabuawala, Tahera ; Chen, Joy ; Cho, Yoon-Jae ; Luong, Richard ; Tamayo, Pablo ; Salih, Tarek ; Aziz, Khaled ; Adam, Stacey J ; Vicent, Silvestre ; Nielsen, Carsten Haagen ; Withofs, Nadia ; Sweet-Cordero, Alejandro ; Gambhir, Sanjiv S ; Rudin, Charles M ; Felsher, Dean W. / Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis. In: P L o S Genetics (Online). 2012 ; Vol. 8, No. 5. pp. 1-10.

Bibtex

@article{cb71571b82f24c8abca26504a22f03a4,
title = "Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis",
abstract = "KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with Kras(G12D) to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy.",
author = "Tran, {Phuoc T} and Shroff, {Emelyn H} and Burns, {Timothy F} and Saravanan Thiyagarajan and Das, {Sandhya T} and Tahera Zabuawala and Joy Chen and Yoon-Jae Cho and Richard Luong and Pablo Tamayo and Tarek Salih and Khaled Aziz and Adam, {Stacey J} and Silvestre Vicent and Nielsen, {Carsten Haagen} and Nadia Withofs and Alejandro Sweet-Cordero and Gambhir, {Sanjiv S} and Rudin, {Charles M} and Felsher, {Dean W}",
year = "2012",
month = may,
day = "24",
doi = "10.1371/journal.pgen.1002650",
language = "English",
volume = "8",
pages = "1--10",
journal = "P L o S Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "5",

}

RIS

TY - JOUR

T1 - Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis

AU - Tran, Phuoc T

AU - Shroff, Emelyn H

AU - Burns, Timothy F

AU - Thiyagarajan, Saravanan

AU - Das, Sandhya T

AU - Zabuawala, Tahera

AU - Chen, Joy

AU - Cho, Yoon-Jae

AU - Luong, Richard

AU - Tamayo, Pablo

AU - Salih, Tarek

AU - Aziz, Khaled

AU - Adam, Stacey J

AU - Vicent, Silvestre

AU - Nielsen, Carsten Haagen

AU - Withofs, Nadia

AU - Sweet-Cordero, Alejandro

AU - Gambhir, Sanjiv S

AU - Rudin, Charles M

AU - Felsher, Dean W

PY - 2012/5/24

Y1 - 2012/5/24

N2 - KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with Kras(G12D) to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy.

AB - KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with Kras(G12D) to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy.

U2 - 10.1371/journal.pgen.1002650

DO - 10.1371/journal.pgen.1002650

M3 - Journal article

C2 - 22654667

VL - 8

SP - 1

EP - 10

JO - P L o S Genetics

JF - P L o S Genetics

SN - 1553-7390

IS - 5

ER -

ID: 40245868