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Review
. 2020 Jan 6;219(1):e201911053.
doi: 10.1083/jcb.201911053.

Stem cells in cancer initiation and progression

Jeevisha Bajaj  1   2   3   4 , Emily Diaz  1   2   3   4 , Tannishtha Reya  1   2   3   4
Affiliations
Review

Stem cells in cancer initiation and progression

Jeevisha Bajaj et al. J Cell Biol. .

Abstract

While standard therapies can lead to an initial remission of aggressive cancers, they are often only a transient solution. The resistance and relapse that follows is driven by tumor heterogeneity and therapy-resistant populations that can reinitiate growth and promote disease progression. There is thus a significant need to understand the cell types and signaling pathways that not only contribute to cancer initiation, but also those that confer resistance and drive recurrence. Here, we discuss work showing that stem cells and progenitors may preferentially serve as a cell of origin for cancers, and that cancer stem cells can be key in driving the continued growth and functional heterogeneity of established cancers. We also describe emerging evidence for the role of developmental signals in cancer initiation, propagation, and therapy resistance and discuss how targeting these pathways may be of therapeutic value.

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Figures

Figure 1.
Figure 1.
Normal and CSC hierarchy. Normal stem cells and CSCs can self-renew and differentiate into more mature cells. (A) Normal stem cells generate the progenitors and mature tissues of the body while CSCs generate more cancer cells. (B) Tumors treated with chemotherapy can leave residual chemoresistant CSCs that can regrow a tumor, whereas CSC targeted therapy may lead to tumor regression and eventual resolution.
Figure 2.
Figure 2.
The origin of cancers. (A) Cancer can be driven by a variety of changes such as genetic mutations, genome instability, and heterochromatin changes. (B) These changes often arise in populations such as stem cells or more mature progenitor cells.
Figure 3.
Figure 3.
Signals sustaining CSCs. Cancer cells are sustained by developmental signaling pathways and interactions with the niche. ABC, ATP binding cassette; HNSCC, head and neck squamous cell carcinoma; LRP, lipoprotein receptor–related protein; NSCLC, non-small-cell lung carcinoma.
Figure 4.
Figure 4.
The normal and malignant stem cell niche. Stem cell interactions with the microenvironment lead to changes in the niche that promote cancer progression. (A and C) Normal stem cells reside in niches guided by complex signaling to control their activation and proliferation. (B) LSCs induce cell death and aberrant signaling within the bone marrow microenvironment. (D) Solid tumor stem cells reside in dense stroma and transformed cells that protect them from chemotherapy. Boxes represent niche cells in A and B or C and D. OB, osteoblast; EC, endothelial cells; CAR, CXCL12-abundant reticular cells; CAF, cancer-associated fibroblasts; MSC, mesenchymal stromal cells; TAM, tumor-associated macrophages.
See this image and copyright information in PMC

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