The transcriptional repressor Snail promotes mammary tumor recurrence

Slides:



Advertisements
Similar presentations
Figure 14.4 The Biology of Cancer (© Garland Science 2007) Challenges of Getting In and Getting Out.
Advertisements

Volume 16, Issue 12, Pages (December 2014)
Anandamide inhibits the Wnt/β-catenin signalling pathway in human breast cancer MDA MB 231 cells  Chiara Laezza, Alba D’Alessandro, Simona Paladino, Anna.
Volume 16, Issue 2, Pages (August 2009)
Volume 22, Issue 6, Pages (December 2012)
Volume 14, Issue 1, Pages (July 2008)
Volume 15, Issue 6, Pages (June 2009)
Cancer: Inappropriate Expression of Stem Cell Programs?
Tumor-Derived Jagged1 Promotes Osteolytic Bone Metastasis of Breast Cancer by Engaging Notch Signaling in Bone Cells  Nilay Sethi, Xudong Dai, Christopher.
Volume 12, Issue 6, Pages (December 2007)
Tumor Dissemination: An EMT Affair
Volume 16, Issue 5, Pages (November 2009)
Epithelial-Mesenchymal Transition and the Stem Cell Phenotype
Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT  Zhen-Yu He, San-Gang Wu, Fang Peng,
Volume 5, Issue 2, Pages (August 2009)
Requirement for CDK4 kinase function in breast cancer
Slug Expression in Mouse Skin and Skin Tumors Is Not Regulated by p53
Volume 2, Issue 4, Pages (April 2008)
Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21
Establishment of Endoderm Progenitors by SOX Transcription Factor Expression in Human Embryonic Stem Cells  Cheryle A. Séguin, Jonathan S. Draper, Andras.
HIF-Dependent Antitumorigenic Effect of Antioxidants In Vivo
Volume 14, Issue 3, Pages (September 2008)
Renée van Amerongen, Anton Berns  Cancer Cell 
DAISY: Picking Synthetic Lethals from Cancer Genomes
Volume 8, Issue 6, Pages (December 2005)
The AML Salad Bowl Cancer Cell
Volume 111, Issue 7, Pages (October 2016)
Volume 6, Issue 5, Pages (March 2014)
Radiation resistance and stem-like cells in brain tumors
New Views into the Genetic Landscape of Metastatic Breast Cancer
Treatment with 5-Fluorouracil and Celecoxib Displays Synergistic Regression of Ultraviolet Light B-Induced Skin Tumors  Traci A. Wilgus, Thomas S. Breza,
Volume 20, Issue 6, Pages (December 2011)
Volume 22, Issue 5, Pages (November 2012)
Uc.454 Inhibited Growth by Targeting Heat Shock Protein Family A Member 12B in Non- Small-Cell Lung Cancer  Jun Zhou, Chenghai Wang, Weijuan Gong, Yandan.
Volume 24, Issue 1, Pages (July 2013)
Volume 20, Issue 6, Pages (December 2011)
Volume 133, Issue 4, Pages (May 2008)
Molecular Therapy - Nucleic Acids
Volume 2, Issue 2, Pages (February 2008)
Volume 22, Issue 6, Pages (December 2012)
Volume 5, Issue 5, Pages (December 2013)
Tumor Entrained Neutrophils Inhibit Seeding in the Premetastatic Lung
James V. Alvarez, Denise Perez, Lewis A. Chodosh  Cancer Cell 
Volume 117, Issue 7, Pages (June 2004)
MiR-135b Stimulates Osteosarcoma Recurrence and Lung Metastasis via Notch and Wnt/β-Catenin Signaling  Hua Jin, Song Luo, Yun Wang, Chang Liu, Zhenghao.
Volume 19, Issue 6, Pages (June 2011)
Anke Sparmann, Dafna Bar-Sagi  Cancer Cell 
Volume 22, Issue 3, Pages (September 2012)
In vivo imaging of S-TRAIL-mediated tumor regression and apoptosis
Volume 138, Issue 4, Pages (April 2010)
Volume 8, Issue 6, Pages (December 2010)
Volume 13, Issue 4, Pages (April 2013)
Volume 2, Issue 6, Pages (December 2002)
Volume 15, Issue 3, Pages (March 2009)
Volume 12, Issue 12, Pages (September 2015)
Thomas S. Griffith, Elizabeth L. Broghammer  Molecular Therapy 
Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance  Valeria R. Fantin, Julie St-Pierre,
Volume 13, Issue 4, Pages (April 2008)
Lack of sustained regression of c-MYC-induced mammary adenocarcinomas following brief or prolonged MYC inactivation  Robert B. Boxer, Joanne W. Jang,
Javed Mohammed, Andrew Ryscavage, Rolando Perez-Lorenzo, Andrew J
Volume 26, Issue 1, Pages (January 2018)
Volume 16, Issue 4, Pages (April 2009)
Volume 17, Issue 4, Pages (October 2015)
Volume 14, Issue 3, Pages (September 2008)
Radiation resistance and stem-like cells in brain tumors
E-cadherin synthetic lethal effects operate in vivo in E-cadherin–defective breast tumors. E-cadherin synthetic lethal effects operate in vivo in E-cadherin–defective.
Kyoung Eun Lee, Dafna Bar-Sagi  Cancer Cell 
Molecular Therapy - Nucleic Acids
The AML Salad Bowl Cancer Cell
Yasuhiro Yamada, Hitomi Aoki, Takahiro Kunisada, Akira Hara 
Presentation transcript:

The transcriptional repressor Snail promotes mammary tumor recurrence Susan E. Moody, Denise Perez, Tien-chi Pan, Christopher J. Sarkisian, Carla P. Portocarrero, Christopher J. Sterner, Kathleen L. Notorfrancesco, Robert D. Cardiff, Lewis A. Chodosh  Cancer Cell  Volume 8, Issue 3, Pages 197-209 (September 2005) DOI: 10.1016/j.ccr.2005.07.009 Copyright © 2005 Elsevier Inc. Terms and Conditions

Figure 1 Fully regressed neu-induced tumors recur spontaneously following a latent period A: Recurrence-free survival for never-induced MTB/TAN mice (n = 13) and MTB/TAN mice deinduced after developing primary tumors on doxycycline (n = 62) (SD 48, range 27–222). B: Timing of tumor regression and recurrence for individual neu-induced tumors. The time of doxycycline withdrawal (day 0) from tumor-bearing mice is indicated by an arrow. A bracket indicates the range of times (relative to doxycycline withdrawal) at which neu was initially induced by doxycycline treatment. C: Luciferase imaging of tumor-bearing MTB/TAN mice demonstrating that recurrent tumors do not express the TAN transgene in the absence of doxycycline. A mouse with multiple primary tumors (arrows) on doxycycline is shown with (B) and without (A) luciferase activity overlay. The same mouse after full regression of tumors off doxycycline is shown with luciferase activity overlay (C). A second mouse with a recurrent tumor in mammary gland 3R (arrow) lacking luciferase activity is shown in D. Cancer Cell 2005 8, 197-209DOI: (10.1016/j.ccr.2005.07.009) Copyright © 2005 Elsevier Inc. Terms and Conditions

Figure 2 Recurrent tumors display characteristics of epithelial-to-mesenchymal transition A: H&E- and anti-CK8-stained sections from representative MTB/TAN primary (neu-expressing) and MTB/TAN recurrent (neu-negative) tumors demonstrating the transition from epithelial to mesenchymal morphology and marker expression. Magnification, 400×. B: H&E-stained sections of two primary tumor grafts allowed to engraft on doxycycline and biopsied while on doxycycline. Tumors either partially regressed and then resumed growth in the absence of doxycycline (T1) or completely regressed and recurred at the same site (T2). Magnification, 400×. C: Northern analysis of primary and recurrent MTB/TAN tumors for expression of epithelial and mesenchymal markers. rRNA (18S) is shown as a loading control. D: Immunofluorescence (IF) analysis of CK8, E-cadherin, and S100A4 expression in representative primary and recurrent tumors. Magnification, 400×. Cancer Cell 2005 8, 197-209DOI: (10.1016/j.ccr.2005.07.009) Copyright © 2005 Elsevier Inc. Terms and Conditions

Figure 3 Snail is spontaneously upregulated in recurrent mammary tumors and induces EMT in primary neu-induced tumor cells A: Microarray analysis of mean Snail and Slug expression levels in primary and recurrent tumors. Expression levels were significantly different between primary tumors and recurrent tumors for both genes (p = 8 × 10−6 for Snail; p = 0.0001 for Slug). Error bars indicate standard error of the mean. B: Northern analysis of Snail expression in primary, recurrent, and incompletely regressing (Inc. Reg.) tumors. rRNA (28S) is shown as a loading control. C: Western analysis of Snail expression in pk1- and pk1-Snail-infected primary tumor cells. D: Photomicrographs of pk1- and pk1-Snail-infected primary tumor cells showing spindle cell morphology of Snail-expressing cells. E: IF analysis of uninfected primary tumor cells, uninfected recurrent tumor cells, and primary tumor cells infected with pk1 or pk1-Snail. Magnification, 400× (D and E). Cancer Cell 2005 8, 197-209DOI: (10.1016/j.ccr.2005.07.009) Copyright © 2005 Elsevier Inc. Terms and Conditions

Figure 4 Snail promotes the recurrence of neu-induced primary tumors A: H&E-stained sections from tumors formed by pk1- and pk1-Snail-infected tumor cells harvested from mice on doxycycline, and from doxycycline-independent, pk1-Snail-transduced recurrent tumors. Magnification, 400×. B: Luciferase activity levels in pk1 and pk1-Snail tumors in mice on doxycycline, and in pk1-Snail recurrent tumors (Rec) arising after doxycycline withdrawal. n = 6 for each tumor type. Error bars indicate standard error of the mean. C: Recurrence-free survival for mice engrafted with pk1-infected and pk1-Snail-infected primary tumor cells. Mice were removed from doxycycline on day 0 after the injected tumor cells had formed a tumor ∼27 mm3 in size. Recurrence rates were significantly higher in pk1-Snail-infected cells (p < 0.0001). D: IF analysis of tumors formed by pk1- and pk1-Snail-infected tumor cells harvested from mice on doxycycline, and of doxycycline-independent, pk1-Snail-transduced recurrent tumors. Magnification, 400×. Cancer Cell 2005 8, 197-209DOI: (10.1016/j.ccr.2005.07.009) Copyright © 2005 Elsevier Inc. Terms and Conditions

Figure 5 Snail expression predicts decreased relapse-free survival in women with breast cancer Five year relapse-free survival for human tumors with low versus high Snail expression in microarray data sets representing the following. A: Locally advanced human breast cancers (Sorlie et al., 2003); B: lymph node-negative human breast cancers (van’t Veer et al., 2002); C: lymph node-negative, ER-positive, and ER-negative human breast cancers (Wang et al., 2005); and D: hormone receptor-positive human breast cancers (Ma et al., 2004). Cancer Cell 2005 8, 197-209DOI: (10.1016/j.ccr.2005.07.009) Copyright © 2005 Elsevier Inc. Terms and Conditions