Refining the role for adult stem cells as cancer cells of origin

Abstract

Significant progress has been made to identify the cells at the foundation of tumorigenesis, the cancer cell of origin (CCO). The majority of data points towards resident adult stem cells (ASCs) or primitive progenitors as the CCO for those cancers studied, highlighting the importance of stem cells not only as propagators but also as initiators of cancer. Recent data suggest tumor initiation at the CCOs can be regulated through both intrinsic and extrinsic signals and that the identity of the CCOs and their propensity to initiate tumorigenesis is context dependent. In this review, we summarize some of the recent findings regarding CCOs and solid tumor initiation and highlight its relation with bona fide human cancer.

Metformin and soybean-derived bioactive molecules attenuate the expansion of stem cell-like epithelial subpopulation and confer apoptotic sensitivity in human colon cancer cells

“…Cancer stem cells (CSC) have emerged as attractive therapeutic targets to inhibit tumor initiation, chemo-resistance, and relapse in many cancer types (Paldino et al 2014;Zeuner et al 2014;White and Lowry 2015). According to the CSC hypothesis, a small population of normal stem cells requisite for maintaining tissue homeostasis/renewal can initiate a tumor upon acquiring one or more driver mutations (Chandler 2010).…”

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

“…The presence of CSC fractions represents a common characteristic of other solid tumors as well, such as breast, ovarian, prostate, colorectal, pancreatic, liver and lung cancers, and these cells are currently considered to be responsible for cancer relapse and are resistant to chemotherapy and radiotherapy [3]. The definition of novel treatment strategies able to effectively eradicate these immature cell subpopulations, for instance by promoting their differentiation through activation of differentiation-related signaling pathways, microRNA (miRNA)-mediated alteration and epigenetic differentiation therapies [4][5][6][7], has been regarded as a relevant topic in the field of both basic and translational medical research.…”

The bad seed: Cancer stem cells in tumor development and resistance

“…Several explanations are offered to describe CSC-driven tumor initiation. The accumulation of oncogenic mutations in adult stem cells or progenitor cells is an attractive model for explaining how cancer initiation and formation occurs in highly proliferative tissues, such as the skin, intestine and hematopoietic system (Fuchs, 2008;Sancho et al, 2004;Seita and Weissman, 2010;White and Lowry, 2015). Another hypothesis suggests that CSCs may arise via a dedifferentiation program, where any differentiated cell can regress from its specialized state and acquire cancer stem-like properties (Visvader, 2011).…”

“…We refer the reader to insightful reviews on the origin of cancer cells (Visvader, 2011;White and Lowry, 2015).…”

“…Activated Smo causes destabilization of Gli transcription factors, leading to transcription of Hh-targeted genes (Ruiz i Altaba, 2011). Excessive Shh signaling has been implicated in a range of cancers and contributes significantly to the long-term self-renewal property of colon, breast and chronic myeloid leukemia (CML) CSCs (Clement et al, 2007; Liu et al, 2006b; Zhao et al, 2009).The Notch signaling pathway plays a general role in controlling specification and pattern formation during the development of most tissues, as well as contributing to the continuous renewal of the intestine, skin and hematopoietic system(Fuchs, 2008;Sancho et al, 2004;Seita and Weissman, 2010;White and Lowry, 2015). In Notch signaling, post-translational modifications result in the formation of a Notch receptor.…”