Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells

Walter, Karolin; Rodriguez-Aznar, Eva; Ferreira, Mónica S. Ventura; Frappart, Pierre‐Olivier; Dittrich, T; Tiwary, Kanishka; Meessen, Sabine; Lerma, L.; Daiss, Nora; Schulte, Lucas-Alexander; Najafova, Zeynab; Arnold, Frank; Usachov, Valentyn; Azoitei, Ninel; Erkan, Mert; Lechel, André; Bruemmendorf, Tim H.; Seufferlein, Thomas; Kleger, Alexander; Tabarés, E.; Güneş, Çagatay; Johnsen, Steven A.; Beier, Fabian; Sáinz, Bruno; Hermann, Patrick C.

doi:10.3390/cancers13133145

Cited by 16 publications

(18 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also essential to consider the intrinsic phenotypic plasticity of stem-like cancer cells via spontaneous activation of one or more of the well-known pluripotency factors (OCT4, KLF4, c-MYC. ; and SOX2) [ 95 , 96 ]. In this context, the role of the CSCs’ niche is crucial, since it regulates the transition between stem and non-stem cell states.…”

Section: Cscs In Tumor Growth and Dissemination: The Quiescent And Th...mentioning

confidence: 99%

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Aramini

Masciale

Grisendi

et al. 2022

Cancers

View full text Add to dashboard Cite

Emerging evidence suggests that a small subpopulation of cancer stem cells (CSCs) is responsible for initiation, progression, and metastasis cascade in tumors. CSCs share characteristics with normal stem cells, i.e., self-renewal and differentiation potential, suggesting that they can drive cancer progression. Consequently, targeting CSCs to prevent tumor growth or regrowth might offer a chance to lead the fight against cancer. CSCs create their niche, a specific area within tissue with a unique microenvironment that sustains their vital functions. Interactions between CSCs and their niches play a critical role in regulating CSCs’ self-renewal and tumorigenesis. Differences observed in the frequency of CSCs, due to the phenotypic plasticity of many cancer cells, remain a challenge in cancer therapeutics, since CSCs can modulate their transcriptional activities into a more stem-like state to protect themselves from destruction. This plasticity represents an essential step for future therapeutic approaches. Regarding self-renewal, CSCs are modulated by the same molecular pathways found in normal stem cells, such as Wnt/β-catenin signaling, Notch signaling, and Hedgehog signaling. Another key characteristic of CSCs is their resistance to standard chemotherapy and radiotherapy treatments, due to their capacity to rest in a quiescent state. This review will analyze the primary mechanisms involved in CSC tumorigenesis, with particular attention to the roles of CSCs in tumor progression in benign and malignant diseases; and will examine future perspectives on the identification of new markers to better control tumorigenesis, as well as dissecting the metastasis process.

show abstract

Section: Cscs In Tumor Growth and Dissemination: The Quiescent And Th...mentioning

confidence: 99%

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Aramini

Masciale

Grisendi

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…It has been shown that also other ALDH enzymes are activated both in SCs and CSCs, including ALDH2*2 (with an association between alcoholism and alcohol-induced cancer risk), ALDH4A1 (activated through p53 and DNA damage), and ALDH7A1 (putatively involved in the regulation of cell cycle) ( 1 ). Furthermore, high ALDH activity, combined with high telomerase activity and the presence of ATP-binding cassette (ABC) transporter G2 (ABCG2), is considered as a universal stem cell marker ( 30 , 31 ). Indeed, a specific and widely used assay to measure ALDH activity called “aldefluor assay” has been originally used for the isolation of hematopoietic stem cells and now is commonly used for the CSCs isolation in many cancers ( 21 , 32 ).…”

Section: Aldehyde Dehydrogenases In Normal and Cancer Stem Cellsmentioning

confidence: 99%

Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance

et al. 2022

View full text Add to dashboard Cite

Aldehyde dehydrogenases (ALDHs) are a family of detoxifying enzymes often upregulated in cancer cells and associated with therapeutic resistance. In humans, the ALDH family comprises 19 isoenzymes active in the majority of mammalian tissues. Each ALDH isoform has a specific differential expression pattern and most of them have individual functional roles in cancer. ALDHs are overexpressed in subpopulations of cancer cells with stem-like features, where they are involved in several processes including cellular proliferation, differentiation, detoxification and survival, participating in lipids and amino acid metabolism and retinoic acid synthesis. In particular, ALDH enzymes protect cancer cells by metabolizing toxic aldehydes in less reactive and more soluble carboxylic acids. High metabolic activity as well as conventional anticancer therapies contribute to aldehyde accumulation, leading to DNA double strand breaks (DSB) through the generation of reactive oxygen species (ROS) and lipid peroxidation. ALDH overexpression is crucial not only for the survival of cancer stem cells but can also affect immune cells of the tumour microenvironment (TME). The reduction of ROS amount and the increase in retinoic acid signaling impairs immunogenic cell death (ICD) inducing the activation and stability of immunosuppressive regulatory T cells (Tregs). Dissecting the role of ALDH specific isoforms in the TME can open new scenarios in the cancer treatment. In this review, we summarize the current knowledge about the role of ALDH isoforms in solid tumors, in particular in association with therapy-resistance.

show abstract

“…In this sense, it has been demonstrated that pancreatic CSCs show longer telomeres and higher telomerase activity than bulk tumor cells, which is related to the expression of pluripotency genes (Nanog, Sox2, Oct3/4). Furthermore, it was confirmed that telomerase inhibition results in pancreatic CSC apoptosis, making this a suitable therapy against CSCs, specifically in pancreatic cancer [11]. Importantly, although telomere shortening is associated with DNA instability and cell senescence [12], it is a process observed in cancer initiation which is then followed by telomere lengthening for chromosome stabilization and tumor progression [13].…”

Section: Gcsc and The Hierarchical Model Of Tumor Progression: Functi...mentioning

confidence: 91%

The cross talk between gastric cancer stem cells and the immune microenvironment: a tumor-promoting factor

et al. 2021

View full text Add to dashboard Cite

Cross talk between cancer cells and the immune system is determinant for cancer progression. Emerging evidence demonstrates that GC characteristics such as metastasis, treatment resistance, and disease recurrence are associated with a tumor subpopulation called gastric cancer stem cells (GCSCs). However, the specific interaction between GCSCs and the immune microenvironment is still under investigation. Although immune evasion has been well described for cancer stem cells (CSCs), recent studies show that GCSCs can also regulate the immune system and even benefit from it. This review will provide an overview of bidirectional interactions between CSCs and immune cells in GC, compiling relevant data about how CSCs can induce leukocyte reprogramming, resulting in pro-tumoral immune cells that orchestrate promotion of metastasis, chemoresistance, tumorigenicity, and even increase in number of cancer cells with stem properties. Some immune cells studied are tumor-associated macrophages (TAMs), neutrophils, Th17 and T regulatory (Treg) cells, mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs), as well as the signaling pathways involved in these pro-tumoral activities. Conversely, although there are cytotoxic leukocytes that can potentially eliminate GCSCs, we describe mechanisms for immune evasion in GCSCs and their clinical implications. Furthermore, we describe current available immunotherapy targeting GCSC-related markers as possible treatment for GC, discussing how the CSC-modified immune microenvironment can mitigate or inactivate these immunotherapies, limiting their effectiveness. Finally, we summarize key concepts and relevant evidence to understand the cross talk between GCSCs and the immune microenvironment as an important process for effective design of therapies against GCSCs that improve the outcome of patients with GC.

show abstract

Telomerase and Pluripotency Factors Jointly Regulate Stemness in Pancreatic Cancer Stem Cells

Cited by 16 publications

References 45 publications

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

Emerging Roles of Aldehyde Dehydrogenase Isoforms in Anti-cancer Therapy Resistance

The cross talk between gastric cancer stem cells and the immune microenvironment: a tumor-promoting factor

Contact Info

Product

Resources

About