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Cancer Stem Cells - Roles and Functions

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Cancer stem cells are cancer cells that have characteristics similar to normal stem cells. However, they specifically give rise to all cell types.

Medically reviewed by

Dr. Rajesh Gulati

Published At May 9, 2023
Reviewed AtOctober 31, 2023


Cancer stem cells or cancer-initiating cells are a type of cell responsible for carcinogenesis. They have distinct proliferation, self-renewal, and differentiation abilities that are thought to be important in cancer initiation, drug resistance, maintenance, progression, and cancer recurrence or metastasis. In addition, factors such as the enhanced capacity of DNA (deoxyribonucleic acid) damage repair, increased activation of drug-efflux pumps, dysregulation of growth and developmental signaling pathways, environmental niche, alterations of cellular metabolism, and impaired apoptotic response are attributed to cancer stem cells in their resistance to the adjuvant chemoradiotherapy to cancer. Therefore, the development of strategies that target cancer stem cells through drug transporters, inhibiting signaling components or pathways, specific surface markers, and destroying their tumor microenvironment has a multifactorial effect that may improve the clinical outcome of the patients.

What Are Stem Cells?

Stem cells are present in multicellular organisms and are distinguished by their ability to self-renew through differentiation and mitotic cell division into a wide variety of specialized cell types. Self-renewal, localization within specialized niches, the ability to give rise to all cell types within an organ, and the generation of cellular progeny are all common properties of stem cells.

What Are Cancer Stem Cells?

Cancer stem cells are a type of tumor cell characterized by self-renewal and clonogenicity. The experimental xenotransplantation technique was used to identify cancer stem cells in leukemia for the first time. Since this discovery, cancer stem cells have been found in a variety of other cancers. In addition, modern assays, such as lineage tracing, enable a better understanding of the prevalence and behavior of these cells. Human prostate stem cells, for example, are thought to be located within the basal epithelium and to give rise to a hierarchy of progenitor cells that can differentiate into neuroendocrine cells.

What Role Do Cancer Stem Cells Play in Tumor Initiation?

Tumors can be initiated by transformed differentiated cells or tissue-resident stem cells. The transformation can occur during tissue regeneration but can also be initiated and accelerated in response to infections, radiations, toxins, or metabolic influences that cause mutations. Oncogenes are overexpressed, and tumor suppressors are inactivated during the transformation process, promoting uncontrolled cell growth. As a result, cells dedifferentiate. Stem cells have unlimited growth potential, and it is thought that stem cell and progeny transformation requires only a few genomic changes. The low mutagenic changes found in more than 10 percent of gastric cancers, for example, suggest that these tumors arise from tissue-resident stem cell populations.

How Similar Are Stem Cells and Cancer Cells?

There are numerous similarities between stem cells and tumor cells. Each requires a signaling pathway and self-renewal that regulates this process, which has been linked to cancers in various organs. Notch and Sonic hedgehog pathways are involved in NSC maintenance and have been linked to the development of tumors like gliomas such as glioblastoma multiforme and medulloblastoma. There are two ways to interpret these findings:

  • The cancer cells mimic the mechanisms of self-renewal found in stem cells.

  • The stem cells are predisposed to becoming tumorigenic because this machinery is already activated. Because cell transformation is possible anywhere along a given lineage that is from stem cell to mature cell, both processes are likely.

Apart from proliferation, other similarities between the cancer cells and the stem cells include the ability to generate new tissues and the ability of stem cells and cancer cells to give rise to phenotypically diverse progeny, as evidenced by the heterogeneity of cells that comprise those tissues. The term cancer stem cell appears to imply that there is a stem cell that is carcinogenic in and of itself; that is, a stem cell or progenitor is the cell of origin. Although this is true in many tumors, cancer stem cells means that certain tumors contain within their population a self-renewing cell capable of not only renewing itself but also renewing the tumor, and thus shares characteristics with stem cells.

What Are the Functions of Cancer Stem Cells?

Multiple regulatory networks, including cytokines from the cancer cell microenvironment, tightly control cancer stem cell differentiation. Several signaling pathways that control cancer, including the Notch and Hedgehog, have previously been reviewed. Wnt gene signaling is important in regulating developmental programs as well as stem cell function.

In mice, increased Wnt signaling causes pituitary tumors, and Wnt drives symmetrical cell divisions in stem cells. The Wnt gene family produces cysteine-rich secreted glycoproteins that bind to frizzled (Fzd) receptors. Wnt binding to Fzd activates disheveled (Dsh), inactivating GSK3, stabilizing -catenin, and thereby inducing target genes such as cyclin D1. The second receptor type related to the low-density lipoprotein (LDL) receptor, known as LRP, also binds Wnt together, inducing canonical Wnt-β-catenin signaling. Dickkopf binds to and represses LRP. In non-canonical Wnt signaling, Wnt binds Fzd and glypican to activate Dsh and thereby Rho and JNK or Ca+2 influx, NFAT, PKA, and CamkII. An additional non-canonical pathway relevant to this review is the planar cell polarity pathway (PCP) which drives symmetric cell division by enhancing the planar polarization of stem cells. In this regard, Wnt7a stimulated the symmetric expansion of satellite stem cells via Fzd7 and Vangl2.


Cancer stem cells are a type of tumor cell that can initiate tumors and cause relapses. Cancer stem cells arise from differentiated cells or adult tissue-resident stem cells at the time of tumor initiation. Because of their significance, several biomarkers that distinguish CSCs have been identified and linked to diagnosis, therapy, and prognosis.

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Dr. Rajesh Gulati
Dr. Rajesh Gulati

Family Physician


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