Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling

Catalano, Veronica; Dentice, Monica; Ambrosio, Raffaele; Luongo, Cristina; Carollo, Rosachiara; Benfante, Antonina; Todaro, Matilde; Stassi, Giorgio; Salvatore, Domenico

doi:10.1158/0008-5472.can-15-1542

Cited by 73 publications

(45 citation statements)

References 25 publications

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“…Even more intriguingly, a recent work (Catalano et al 2016) showed that T 3 treatment induces differentiation of colorectal cancer stem cells (CR-CSCs), by increasing the levels of the bone morphogenetic protein (BMP4, a known promoter of differentiation in normal colonic epithelium) and of its downstream targets. The same work also showed that increasing intracellular levels of T 3 results in reduced 23:8 clonogenic and tumourigenic potential and establishes a higher sensitivity of CR-CSCs to chemotherapy, supporting the hypothesis that T 3 may inhibit tumour development by activating a differentiation program.…”

Section: T 3 /Trs Axis and Cell Differentiationmentioning

confidence: 99%

T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair

Perra

Plateroti

Columbano

2016

Endocrine-Related Cancer

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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its burden is expected to further increase in the next years. Chronic inflammation, induced by multiple viruses or metabolic alterations, and epigenetic and genetic modifications, cooperate in cancer development via a combination of common and distinct aetiology-specific pathways. In spite of the advances of classical therapies, the prognosis of this neoplasm has not considerably improved over the past few years. The advent of targeted therapies and the approval of the systemic treatment of advanced HCC with the kinase inhibitor sorafenib have provided some hope for the future. However, the benefits obtained from this treatment are still disappointing, as it extends the median life expectancy of patients by only few months. It is thus mandatory to find alternative effective treatments. Although the role played by thyroid hormones (THs) and their nuclear receptors (TRs) in human cancer is still unclear, mounting evidence indicates that they behave as oncosuppressors in HCC. However, the molecular mechanisms by which they exert this effect and the consequence of their activation following ligand binding on HCC progression remain elusive. In this review, we re-evaluate the existing evidence of the role of TH/TRs in HCC development; we will also discuss how TR alterations could affect fundamental biological processes, such as hepatocyte proliferation and differentiation, and consequently HCC progression. Finally, we will discuss if and how TRs can be foreseen as therapeutic targets in HCC and whether selective TR modulation by TH analogues may hold promise for HCC treatment.

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Section: T 3 /Trs Axis and Cell Differentiationmentioning

confidence: 99%

T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair

Perra

Plateroti

Columbano

2016

Endocrine-Related Cancer

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“…There are several other signaling pathways which have important contribution to CSC maintenance (schematic representation in Figure 1). The role of Notch [27, 28], TGF-beta [29, 30], and Wnt [31, 32] in CSC maintenance has been extensively reported. These molecules are also in clinical trials to aid in radiation therapy.…”

Section: Cscs and Molecular Mechanisms Regulating Radiation Responsementioning

confidence: 99%

Cancer Stem Cells and Radioresistance: Rho/ROCK Pathway Plea Attention

Pranatharthi

Ross

Srivastava

2016

Stem Cells International

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Radiation is the most potent mode of cancer therapy; however, resistance to radiation therapy results in tumor relapse and subsequent fatality. The cancer stem cell (CSC), which has better DNA repair capability, has been shown to contribute to tumor resistance and is an important target for treatment. Signaling molecules such as Notch, Wnt, and DNA repair pathways regulate molecular mechanisms in CSCs; however, none of them have been translated into therapeutic targets. The RhoGTPases and their effector ROCK-signaling pathway, though important for tumor progression, have not been well studied in the context of radioresistance. There are reports that implicate RhoA in radioresistance. ROCK2 has also been shown to interact with BRCA2 in the regulation of cell division. Incidentally, statins (drug for cardiovascular ailment) are functional inhibitors of RhoGTPases. Studies suggest that patients on statins have a better prognosis in cancers. Data from our lab suggest that ROCK signaling regulates radioresistance in cervical cancer cells. Collectively, these findings suggest that Rho/ROCK signaling may be important for radiation resistance. In this review, we enumerate the role of Rho/ROCK signaling in stemness and radioresistance and highlight the need to explore these molecules for a better understanding of radioresistance and development of therapeutics.

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“…5) [48]. Recently, this hypothesis has been again supported by Catalano and coworkers [28], who have found that increased intracellular TH concentration through D3 depletion induces cell differentiation and sharply mitigates tumor formation.…”

Section: Reviewmentioning

confidence: 87%

E-cadherin roles in animal biology: A perspective on thyroid hormone-influence

Izaguirre

Casco

2016

Cell Commun Signal

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The establishment, remodeling and maintenance of tissular architecture during animal development, and even across juvenile to adult life, are deeply regulated by a delicate interplay of extracellular signals, cell membrane receptors and intracellular signal messengers. It is well known that cell adhesion molecules (cell-cell and cell-extracellular matrix) play a critical role in these processes. Particularly, adherens junctions (AJs) mediated by E-cadherin and catenins determine cell-cell contact survival and epithelia function. Consequently, this review seeks to encompass the complex and prolific knowledge about E-cadherin roles during physiological and pathological states, particularly focusing on the influence exerted by the thyroid hormone (TH).

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Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling

Cited by 73 publications

References 25 publications

T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair

T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair

Cancer Stem Cells and Radioresistance: Rho/ROCK Pathway Plea Attention

E-cadherin roles in animal biology: A perspective on thyroid hormone-influence

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