Using MKK4’s metastasis suppressor function to identify and dissect cancer cell–microenvironment interactions during metastatic colonization
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- 作者：Venkatesh Krishnan (1)
Nathan Stadick (1)
Robert Clark (2)
Russell Bainer (3)
Jennifer T. Veneris (4)
Shaheena Khan (1) (7)
Angela Drew (5)
Carrie Rinker-Schaeffer (1) (6) - 关键词：Metastasis suppressors ; MKK4 ; Parallel progression model ; Omentum ; Microenvironment ; Cancer evolution ; Milky spots
- 刊名：Cancer and Metastasis Reviews
- 出版年：2012
- 出版时间：4 - December 2012
- 年：2012
- 卷：31
- 期：3
- 页码：605-613
- 全文大小：564KB
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Nathan Stadick (1)
Robert Clark (2)
Russell Bainer (3)
Jennifer T. Veneris (4)
Shaheena Khan (1) (7)
Angela Drew (5)
Carrie Rinker-Schaeffer (1) (6)
1. The Section of Urology, Department of Surgery, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL, 60637, USA
2. Department of Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL, USA
3. Department of Human Genetics, The University of Chicago, Chicago, IL, USA
4. The Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA
7. Armour Academic Center, Rush Medical College, 600 S. Paulina Street, Suite 202, Chicago, IL, 60612, USA
5. Department of Cancer and Cell Biology Vontz Center for Molecular Studies, University of Cincinnati, 3125 Eden Avenue, Cincinnati, OH, 45267-0521, USA
6. The Committee on Cancer Biology, The University of Chicago, Chicago, IL, USA - ISSN：1573-7233
文摘
Host tissue microenvironment plays key roles in cancer progression and colonization of secondary organs. One example is ovarian cancer, which colonizes the peritoneal cavity and especially the omentum. Our research indicates that the interaction of ovarian cancer cells with the omental microenvironment can activate a stress-kinase pathway involving the mitogen-activated protein kinase kinase 4 (MKK4). A combination of clinical correlative and functional data suggests that MKK4 activation suppresses growth of ovarian cancer cells lodged in omentum. These findings prompted us to turn our focus to the cellular composition of the omental microenvironment and its role in regulating cancer growth. In this review, in addition to providing an overview of MKK4 function, we highlight a use for metastasis suppressors as a molecular tool to study cancer cell interaction with its microenvironment. We review features of the omentum that makes it a favorable microenvironment for metastatic colonization. In conclusion, a broader, evolutionary biology perspective is presented which we believe needs to be considered when studying the evolution of cancer cells within a defined microenvironment. Taken together, this approach can direct new multi-dimensional lines of research aimed at a mechanistic understanding of host tissue microenvironment, which could be used to realize novel targets for future research.