Wnt signaling in cancer stem cells and colon cancer metastasis

Overactivation of Wnt signaling is a hallmark of colorectal cancer (CRC). The Wnt pathway is a key regulator of both the early and the later, more invasive, stages of CRC development. In the normal intestine and colon, Wnt signaling controls the homeostasis of intestinal stem cells (ISCs) that fuel, via proliferation, upward movement of progeny cells from the crypt bottom toward the villus and differentiation into all cell types that constitute the intestine. Studies in recent years suggested that cancer stem cells (CSCs), similar to ISCs of the crypts, consist of a small subpopulation of the tumor and are responsible for the initiation and progression of the disease. Although various ISC signature genes were also identified as CRC markers and some of these genes were even demonstrated to have a direct functional role in CRC development, the origin of CSCs and their contribution to cancer progression is still debated. Here, we describe studies supporting a relationship between Wnt-regulated CSCs and the progression of CRC.

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The effects of mutant Ras proteins on the cell signalome

Cancer and Metastasis Reviews ◽

10.1007/s10555-020-09912-8 ◽

2020 ◽

Vol 39 (4) ◽

pp. 1051-1065 ◽

Cited By ~ 1

Author(s):

Tamás Takács ◽

Gyöngyi Kudlik ◽

Anita Kurilla ◽

Bálint Szeder ◽

László Buday ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Signaling Pathways ◽

Cancer Progression ◽

Cell Types ◽

Genetic Alterations ◽

Signaling Networks ◽

Specific Cell ◽

Ras Proteins ◽

Ras Genes

AbstractThe genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including the RAC/PAK, RalGDS/Ral, and PKC/PLC signaling pathways. Moreover, microRNA-regulated Ras-associated signaling pathways are also discussed to highlight the importance of Ras regulation in cancer. Finally, emerging data show that the signal alterations in specific cell types, such as cancer stem cells, could promote cancer development. Therefore, we also cover the up-to-date findings related to Ras-regulated signal transduction in cancer stem cells.

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Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892816666210208232251 ◽

2021 ◽

Vol 16 ◽

Author(s):

Dunne Fong ◽

Chase T. Christensen ◽

Marion M. Chan

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Cancer Care ◽

Cancer Metastasis ◽

Psychotic Disorders ◽

Inflammatory Diseases ◽

Fatal Outcome ◽

Cell Types ◽

Repurposed Drugs

Background: Cancer is a multistep process involving genetic and epigenetic changes in the somatic genome. Genetic mutations as well as environmental factors lead to the initiation, promotion, and progression of cancer. Metastasis allows cancer cells to spread via circulatory and lymphatic systems; secondary tumorigenesis typically leads to a fatal outcome. Recent experimental evidence suggests Cancer Stem Cells (CSCs) play a pivotal role in tumor progression. A tumor is heterogeneous and composed of different cell types. CSCs are a subpopulation of tumor cells possessing abilities to self-renew and differentiate. Objective: To present repurposed drugs, and potential candidates, that can serve as anticancer medications intended to target resistant cancer cells, i.e. CSCs. Methods: Research publications, FDA filings, and patents have been reviewed for repurposed drugs or drug combinations that can act to improve cancer care. Results: Drugs that act against CSCs include ones approved for treatment of diabetes (metformin & thiazolidinediones), parasitic diseases (chloroquine, niclosamide, mebendazole & pyrvinium), psychotic disorders (thioridazine, clomipramine & phenothiazines), alcoholism (disulfiram), lipid disorder (statins), inflammatory diseases (tranilast, auranofin, acetaminophen & celecoxib), antibiotics (azithromycin), and other disorders. Current research findings advocate the existence of beneficial effects by combining these repurposed drugs, and also through their complementary use with conventional cancer therapies. Conclusion: Repurposing FDA-approved medications towards cancer care, by targeting the resistant CSCs, will allow for a quicker, cheaper development and approval process. A larger drug library available to physicians will allow for increased efficacy during both first-line and recurrent cancer treatments.

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Hypoxia and Inflammation in Prostate Cancer Progression. Cross-talk with Androgen and Estrogen Receptors and Cancer Stem Cells

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530316666161130160144 ◽

2017 ◽

Vol 16 (4) ◽

pp. 235-248 ◽

Cited By ~ 5

Author(s):

Matteo Russo ◽

Linda Ravenna ◽

Laura Pellegrini ◽

Elisa Petrangeli ◽

Luisa Salvatori ◽

...

Keyword(s):

Prostate Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Estrogen Receptors ◽

Cancer Progression ◽

Cross Talk ◽

Prostate Cancer Progression

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The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽

10.3390/cancers13061239 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1239

Author(s):

Leila Jahangiri ◽

Tala Ishola ◽

Perla Pucci ◽

Ricky M. Trigg ◽

Joao Pereira ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Progression ◽

Regulatory Networks ◽

Epithelial To Mesenchymal Transition ◽

Tumour Microenvironment ◽

Repair Capacity ◽

Mesenchymal Transition ◽

Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

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αSMA+ fibroblasts suppress Lgr5+ cancer stem cells and restrain colorectal cancer progression

Oncogene ◽

10.1038/s41388-021-01866-7 ◽

2021 ◽

Author(s):

Kathleen M. McAndrews ◽

Karina Vázquez-Arreguín ◽

Changsoo Kwak ◽

Hikaru Sugimoto ◽

Xiaofeng Zheng ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Progression ◽

Colorectal Cancer Progression

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Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells

Cancer Gene Therapy ◽

10.1038/cgt.2016.3 ◽

2016 ◽

Vol 23 (4) ◽

pp. 83-89 ◽

Cited By ~ 41

Author(s):

X Sun ◽

C Xu ◽

S-C Tang ◽

J Wang ◽

H Wang ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Wnt Signaling ◽

Breast Cancer Stem Cells ◽

Self Renewal

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Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor-Mesenchymal Stem Cell Interaction for therapeutic interventions

Current Drug Targets ◽

10.2174/1389450122666210824142247 ◽

2021 ◽

Vol 22 ◽

Author(s):

Soheila Montazersaheb ◽

Ezzatollah Fathi ◽

Ayoub Mamandi ◽

Raheleh Farahzadi ◽

Hamid Reza Heidari

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tumor Microenvironment ◽

Cancer Stem Cells ◽

Tumor Cells ◽

Cell Types ◽

Cell Interaction ◽

Therapeutic Interventions ◽

Tumorigenic Potential ◽

Different Types

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

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