Sox2 cooperates with inflammation-mediated stat3 activation in the malignant transformation of foregut basal progenitor cells

Kuancan Liu; Ming Jiang; Yun Lu; Hao Chen; Jun Sun; Shaoping Wu; Wei Yao Ku; Hiroshi Nakagawa; Yoshiaki Kita; Shoji Natsugoe; Jeffrey H. Peters; Anil Rustgi; Mark W. Onaitis; Amy Kiernan; Xiaoxin Chen; Jianwen Que

doi:10.1016/j.stem.2013.01.007

Sox2 cooperates with inflammation-mediated stat3 activation in the malignant transformation of foregut basal progenitor cells

Kuancan Liu, Ming Jiang, Yun Lu, Hao Chen, Jun Sun, Shaoping Wu, Wei Yao Ku, Hiroshi Nakagawa, Yoshiaki Kita, Shoji Natsugoe, Jeffrey H. Peters, Anil Rustgi, Mark W. Onaitis, Amy Kiernan, Xiaoxin Chen, Jianwen Que

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Abstract

Sox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment- activated Stat3 is required for Sox2-driven tumorigenesis.

Original language	English (US)
Pages (from-to)	304-315
Number of pages	12
Journal	Cell Stem Cell
Volume	12
Issue number	3
DOIs	https://doi.org/10.1016/j.stem.2013.01.007
State	Published - Mar 7 2013
Externally published	Yes

Bibliographical note

Funding Information:
This work was initiated in Dr. Brigid Hogan’s laboratory at the Department of Cell Biology, Duke University. We are grateful to Dr. Brigid Hogan and Dr. Mark Noble, Dr. Hartmut Land, Dr. Craig Jordan, and Dr. Dirk Bohmann at the Department of Biomedical Genetics in the University of Rochester for helpful discussion and critical reading of the manuscript. We also wish to thank Ian Jacobs and other members of the Que laboratory for discussion and technical assistance. This work was supported by the following grants: NIDDK K99/R00 DK082650 (J.Q.), NCI U54 CA156735 (X.C.), NCI P01-CA098101 (and its Molecular Pathology/Imaging and Molecular Biology Core Facilities, A.R.), NCI U01-CA143056 (A.R.), and American Cancer Society (A.R.).

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Liu, K., Jiang, M., Lu, Y., Chen, H., Sun, J., Wu, S., Ku, W. Y., Nakagawa, H., Kita, Y., Natsugoe, S., Peters, J. H., Rustgi, A., Onaitis, M. W., Kiernan, A., Chen, X., & Que, J. (2013). Sox2 cooperates with inflammation-mediated stat3 activation in the malignant transformation of foregut basal progenitor cells. Cell Stem Cell, 12(3), 304-315. https://doi.org/10.1016/j.stem.2013.01.007

Liu, K, Jiang, M, Lu, Y, Chen, H, Sun, J, Wu, S, Ku, WY, Nakagawa, H, Kita, Y, Natsugoe, S, Peters, JH, Rustgi, A, Onaitis, MW, Kiernan, A, Chen, X & Que, J 2013, 'Sox2 cooperates with inflammation-mediated stat3 activation in the malignant transformation of foregut basal progenitor cells', Cell Stem Cell, vol. 12, no. 3, pp. 304-315. https://doi.org/10.1016/j.stem.2013.01.007

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title = "Sox2 cooperates with inflammation-mediated stat3 activation in the malignant transformation of foregut basal progenitor cells",

abstract = "Sox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment- activated Stat3 is required for Sox2-driven tumorigenesis.",

author = "Kuancan Liu and Ming Jiang and Yun Lu and Hao Chen and Jun Sun and Shaoping Wu and Ku, {Wei Yao} and Hiroshi Nakagawa and Yoshiaki Kita and Shoji Natsugoe and Peters, {Jeffrey H.} and Anil Rustgi and Onaitis, {Mark W.} and Amy Kiernan and Xiaoxin Chen and Jianwen Que",

note = "Funding Information: This work was initiated in Dr. Brigid Hogan{\textquoteright}s laboratory at the Department of Cell Biology, Duke University. We are grateful to Dr. Brigid Hogan and Dr. Mark Noble, Dr. Hartmut Land, Dr. Craig Jordan, and Dr. Dirk Bohmann at the Department of Biomedical Genetics in the University of Rochester for helpful discussion and critical reading of the manuscript. We also wish to thank Ian Jacobs and other members of the Que laboratory for discussion and technical assistance. This work was supported by the following grants: NIDDK K99/R00 DK082650 (J.Q.), NCI U54 CA156735 (X.C.), NCI P01-CA098101 (and its Molecular Pathology/Imaging and Molecular Biology Core Facilities, A.R.), NCI U01-CA143056 (A.R.), and American Cancer Society (A.R.). ",

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T1 - Sox2 cooperates with inflammation-mediated stat3 activation in the malignant transformation of foregut basal progenitor cells

AU - Liu, Kuancan

AU - Jiang, Ming

AU - Lu, Yun

AU - Chen, Hao

AU - Sun, Jun

AU - Wu, Shaoping

AU - Ku, Wei Yao

AU - Nakagawa, Hiroshi

AU - Kita, Yoshiaki

AU - Natsugoe, Shoji

AU - Peters, Jeffrey H.

AU - Rustgi, Anil

AU - Onaitis, Mark W.

AU - Kiernan, Amy

AU - Chen, Xiaoxin

AU - Que, Jianwen

N1 - Funding Information: This work was initiated in Dr. Brigid Hogan’s laboratory at the Department of Cell Biology, Duke University. We are grateful to Dr. Brigid Hogan and Dr. Mark Noble, Dr. Hartmut Land, Dr. Craig Jordan, and Dr. Dirk Bohmann at the Department of Biomedical Genetics in the University of Rochester for helpful discussion and critical reading of the manuscript. We also wish to thank Ian Jacobs and other members of the Que laboratory for discussion and technical assistance. This work was supported by the following grants: NIDDK K99/R00 DK082650 (J.Q.), NCI U54 CA156735 (X.C.), NCI P01-CA098101 (and its Molecular Pathology/Imaging and Molecular Biology Core Facilities, A.R.), NCI U01-CA143056 (A.R.), and American Cancer Society (A.R.).

PY - 2013/3/7

Y1 - 2013/3/7

N2 - Sox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment- activated Stat3 is required for Sox2-driven tumorigenesis.

AB - Sox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment- activated Stat3 is required for Sox2-driven tumorigenesis.

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ER -

Sox2 cooperates with inflammation-mediated stat3 activation in the malignant transformation of foregut basal progenitor cells

Abstract

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