Crucial role of glucosylceramide synthase in the regulation of stem cell‐like cancer cells in B16F10 murine melanoma

Since the crucial role of the microenvironment has been highlighted, many studies have been focused on the role of biomechanics in cancer cell growth and the invasion of the surrounding environment. Despite the search in recent years for molecular biomarkers to try to classify and stratify cancers, much effort needs to be made to take account of morphological and nanomechanical parameters that could provide supplementary information concerning tissue complexity adaptation during cancer development. The biomechanical properties of cancer cells and their surrounding extracellular matrix have actually been proposed as promising biomarkers for cancer diagnosis and prognosis. The present review first describes the main methods used to study the mechanical properties of cancer cells. Then, we address the nanomechanical description of cultured cancer cells and the crucial role of the cytoskeleton for biomechanics linked with cell morphology. Finally, we depict how studying interaction of tumor cells with their surrounding microenvironment is crucial to integrating biomechanical properties in our understanding of tumor growth and local invasion.

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Activation of the orphan nuclear receptor RORα counteracts the proliferative effect of fatty acids on prostate cancer cells: Crucial role of 5-lipoxygenase

International Journal of Cancer ◽

10.1002/ijc.20387 ◽

2004 ◽

Vol 112 (1) ◽

pp. 87-93 ◽

Cited By ~ 27

Author(s):

Roberta M. Moretti ◽

Marina Montagnani Marelli ◽

Angelo Sala ◽

Marcella Motta ◽

Patrizia Limonta

Keyword(s):

Prostate Cancer ◽

Fatty Acids ◽

Cancer Cells ◽

Nuclear Receptor ◽

Crucial Role ◽

Orphan Nuclear Receptor ◽

Prostate Cancer Cells ◽

Proliferative Effect

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Ubiquitination and deubiquitination of MCL1 in cancer: deciphering chemoresistance mechanisms and providing potential therapeutic options

Cell Death and Disease ◽

10.1038/s41419-020-02760-y ◽

2020 ◽

Vol 11 (7) ◽

Cited By ~ 2

Author(s):

Xiaowei Wu ◽

Qingyu Luo ◽

Zhihua Liu

Keyword(s):

Clinical Practice ◽

Cancer Cells ◽

Therapeutic Target ◽

Crucial Role ◽

Ubiquitin Proteasome System ◽

Therapeutic Strategies ◽

E3 Ligases ◽

Ubiquitin Proteasome ◽

Specific Inhibitors

Abstract MCL1 is an important antiapoptotic member of the BCL-2 family that is distinguishable from other family members based on its relatively short half-life. Emerging studies have revealed the crucial role of MCL1 in the chemoresistance of cancer cells. The antiapoptotic function of MCL1 makes it a popular therapeutic target, although specific inhibitors have begun to emerge only recently. Notably, emerging studies have reported that several E3 ligases and deubiquitinases modulate MCL1 stability, providing an alternate means of targeting MCL1 activity. In addition, the emergence and development of proteolysis-targeting chimeras, the function of which is based on ubiquitination-mediated degradation, has shown great potential. In this review, we provide an overview of the studies investigating the ubiquitination and deubiquitination of MCL1, summarize the latest evidence regarding the development of therapeutic strategies targeting MCL1 in cancer treatment, and discuss the promising future of targeting MCL1 via the ubiquitin–proteasome system in clinical practice.

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The Role of Bone Stem Cell Niches in Bone Metastasis

Applied Sciences ◽

10.3390/app10217713 ◽

2020 ◽

Vol 10 (21) ◽

pp. 7713

Author(s):

Roberto Tamma ◽

Tiziana Annese ◽

Domenico Ribatti

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Bone Metastasis ◽

Cancer Cells ◽

Bone Cells ◽

Metastatic Progression ◽

Therapeutic Approaches ◽

Endosteal Niche ◽

Stem Cell Quiescence

In post-natal life, stem cells contribute to the preservation of many tissues. In adults, stem cells remain localized, in particular, specialized microanatomical areas named as niches, which are crucial in the control of stem cell quiescence and activity through the production of many regulatory signals. Bone physiologically includes both the endosteal niche and the vascular niche, which are involved in the attraction, retention and release of the residing stem cells during the formation of new vessels as well as in the control of the differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts. In tumors, cancer cells are able to take control of the niches to support all the stages of the tumorigenesis, transforming them in the so-called pre-metastatic and metastatic niches. Hence, there is emerging importance of the interactions between cancer cells, bone cells and niches in driving metastatic progression. This review article summarizes the literature data concerning the role of bone vascular and endosteal niches in the regulation of bone metastasis, focusing on their cellular and molecular interactions and the potential therapeutic approaches.

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Abstract 902: Cancer-stem-cell (CSC) marker, DCLK1-S, enhances invasive potential of cancer cells by phosphorylating/activating NFATc2: role of COL3A1 and SPARC in mediating metastatic effects of DCLK1-S/NFATc2

10.1158/1538-7445.am2017-902 ◽

2017 ◽

Author(s):

Malaney O. Connell ◽

Shubhashish Sarkar ◽

Heidi Spratt ◽

Steven Widen ◽

Thomas G. Wood ◽

...

Keyword(s):

Stem Cell ◽

Cancer Stem Cell ◽

Cancer Cells ◽

Invasive Potential

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APRIL and BAFF increase breast cancer cell stemness

10.1101/151902 ◽

2017 ◽

Author(s):

Vasiliki Pelekanou ◽

George Notas ◽

Paraskevi Athanasouli ◽

Konstantinos Alexakis ◽

Fotini Kiagiadaki ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Cancer Stem Cell ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Mesenchymal Transition ◽

Pluripotency Genes

AbstractRecent advances in cancer immunology revealed immune-related properties of cancer cells as novel promising therapeutic targets. The two TNF superfamily members, APRIL and BAFF even though were primarily studied in lymphocyte maturation, they have also been associated with tumor growth and aggressiveness in a number of solid tumors, including breast cancer. In the present work we studied the effect of APRIL and BAFF on epithelial to mesenchymal transition and migration of breast cancer cells, and their action on the sub-population of cancer stem cells identified by autofluorescence and ALDH activity. Their action on an number of pluripotency genes was examined and breast cancer stem cell ability to form mammospheres was also utilized. The receptor and the signaling pathway involved as well as the role of steroid hormones in their action were also investigated. Our findings show that both APRIL and BAFF increase epithelial to mesenchymal transition and migratory capacity of breast cancer cells, as well as cancer stem cell numbers, by inducing pluripotency genes such as KLF4 and NANOG. These effects are mediated by their common receptor BCMA and the JNK signaling pathway. Interestingly, androgens enhance APRIL transcription and subsequently its pluripotency effect. In conclusion, our data support the significant role of APRIL and BAFF in breast cancer disease progression and provide evidence for a new possible mechanism of therapy resistance, that could be particularly relevant in aromatase inhibitors-treated patients, were local androgen is increased.

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Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

Stem Cells International ◽

10.1155/2016/2048731 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 52

Author(s):

Lisa Y. Pang ◽

Emma A. Hurst ◽

David J. Argyle

Keyword(s):

Stem Cell ◽

Cancer Stem Cell ◽

Cancer Cells ◽

Cell Biology ◽

Tumour Growth ◽

Cyclooxygenase 2 ◽

Conventional Chemotherapy ◽

Normal Tissues ◽

Cox 2

Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2), a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

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The Emerging Role of Exosomes in Cancer Chemoresistance

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.737962 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jing Li ◽

Na Gao ◽

Zhengfan Gao ◽

Wei Liu ◽

Bairen Pang ◽

...

Keyword(s):

Drug Resistance ◽

Stem Cell ◽

Cancer Treatment ◽

Cancer Cells ◽

Pathological State ◽

Liquid Biopsies ◽

Specificity And Sensitivity ◽

Drug Removal ◽

Cancer Chemoresistance

Chemoresistance is an impending challenge in cancer treatment. In recent years, exosomes, a subtype of extracellular vesicles with a diameter of 40–150 nm in bloodstream and other bio-fluids, have attracted increasing interest. Exosomes contain proteins, nucleic acids, and lipids, which act as important signaling molecules. Many reports indicate that exosomes play critical roles in chemoresistance through intercellular interactions, including drug removal from cells, transfer of drug resistance phenotypes to other cancer cells, and the increase in plastic stem cell subsets. Exosomes can reflect the physiological and pathological state of parent cells. Owing to their elevated stability, specificity, and sensitivity, exosomes are served as biomarkers in liquid biopsies to monitor cancer chemoresistance, progression, and recurrence. This review summarizes the exosome-mediated mechanisms of cancer chemoresistance, as well as its role in reversing and monitoring chemoresistance. The scientific and technological challenges and future applications of exosomes are also explored.

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