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PTEN in Hematopoietic and Intestinal Stem Cells and Cancer

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Stem Cells and Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

In this chapter, we discuss the roles of the tumor suppressor PTEN in regulating stem cells of the hematopoietic and intestinal systems as well as its contributions to carcinogenesis in these tissues. Stem cells in continually renewing tissues must balance the necessity to maintain their respective tissue with the requirement to preserve the stem cell pool throughout adult life. Hematopoietic stem cells (HSCs) are tasked with sustaining the various cell types of the blood while intestinal stem cells must continually regenerate the gut epithelium. PTEN, a dual-specificity phosphatase able to target proteins and lipids, is the sole antagonist of the PI3K/AKT signaling pathway. PI3K/AKT signaling is often activated by growth factors and typically results in the stimulation of cellular outcomes such as proliferation, inhibition of apoptosis, and migration. Functional studies of PTEN loss in animal models have indicated a role for PTEN as a protective agent for stem cells that promote quiescence, as PTEN-deficient animals exhibit overproliferative stem and progenitor cells and are prone to proliferative disorders and cancer development. However, from these and other studies including accumulated clinical evidence, it is not likely that PTEN acts alone to stimulate malignant transformation. Indeed, HSCs in PTEN-deficient animals become exhausted and unable to sustain a healthy hematopoietic system. Rather, PTEN appears to function as a restrictive factor that prevents unregulated proliferation, which leaves stem and progenitor cells susceptible to additional mutations/deregulation, such as in Wnt/β-catenin signaling, that results in overt cancer. Additional study into PTEN/PI3K/AKT signaling should provide further insight into self-renewal mechanisms of adult stem cells that may aid in distinguishing normal stem cells from their cancer-initiating counterparts.

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  1. Stowers Institute for Medical Research, Kansas City, MO, USA

    Jason T. Ross, David H. Scoville, Xi He & Linheng Li

  2. Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA

    Jason T. Ross

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    Ross, J.T., Scoville, D.H., He, X., Li, L. (2009). PTEN in Hematopoietic and Intestinal Stem Cells and Cancer. In: Teicher, B., Bagley, R. (eds) Stem Cells and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-933-8_5

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