Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells

Sari, Ita Novita; Phi, Lan Thi; Jun, Nayoung; Wijaya, Yoseph Toni; Lee, Sang‐Hyun; Kwon, Hyog Young

doi:10.3390/cells7110208

Cited by 149 publications

(114 citation statements)

References 244 publications

(339 reference statements)

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…Moreover, by combining CSCs, targeted therapies with conventional one tumors could be eradicated [26]. Targeting stemness pathways and microenvironment components while using stemness markers, or immunological approaches are some examples of recent efforts for designing more effective cancer treatments [27,28]. Those strategies have proven to be valid and they limit tumor progression, in addition to the reduction of tumor size [29,30].…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells

Hassan

Afify

Nair

et al. 2019

Cancers

View full text Add to dashboard Cite

Cancer stem cells (CSCs) represent the subpopulation of cancer cells with the ability to differentiate into other cell phenotypes and initiated tumorigenesis. Previously, we reported generating CSCs from mouse induced pluripotent stem cells (miPSCs). Here, we investigated the ability of the CSCs to differentiate into hematopoietic cells. First, the primary cells were isolated from malignant tumors that were formed by the CSCs. Non-adherent cells (NACs) that arose from adherent cells were collected and their viability, as well as the morphology and expression of hematopoietic cell markers, were analyzed. Moreover, NACs were injected into the tail vein of busulfan conditioned Balb/c nude mice. Finally, CSCs were induced to differentiate to macrophages while using IL3 and SCF. The round nucleated NACs were found to be viable, positive for hematopoietic lineage markers and CD34, and expressed hematopoietic markers, just like homing to the bone marrow. When NACs were injected into mice, Wright-Giemsa staining showed that the number of white blood cells got higher than those in the control mice after four weeks. CSCs also showed the ability to differentiate toward macrophages. CSCs were demonstrated to have the potential to provide progenies with hematopoietic markers, morphology, and homing ability to the bone marrow, which could give new insight into the tumor microenvironment according to the plasticity of CSCs.

show abstract

Section: Discussionmentioning

confidence: 99%

Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells

Hassan

Afify

Nair

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…Activation of Hedgehog (Hh) signaling is triggered by the binding of Hh ligands to patched (PTCH) receptors. Interactions of Hh ligands with PTCH receptors stimulate smoothened (SMO) and glioma-associated oncogene (GLI) transcription factors [132,133]. The inhibition of SMO and GLI decreases the number of aldehyde dehydrogenase (ALDH)-positive CSCs in melanoma [134].…”

Section: A Mirna and Hedgehog Signalingmentioning

confidence: 99%

“…In addition, the regulation of ZEB1 expression is mediated by miR-574-3p and miR-708-3p in gastric and breast cancer cells, respectively. Both miRNAs negatively regulate the process of EMT and render cancer cells susceptible to chemotherapy agents [133,167]. In the case of miR-708-3p, it also regulates EMT markers, cadherin 2 (CDH2, also known as N-cadherin) and VIM, by directly binding to their 3 UTRs [133].…”

Section: Mirnas Directly Regulating Emt-related Transcription Factorsmentioning

confidence: 99%

“…Both miRNAs negatively regulate the process of EMT and render cancer cells susceptible to chemotherapy agents [133,167]. In the case of miR-708-3p, it also regulates EMT markers, cadherin 2 (CDH2, also known as N-cadherin) and VIM, by directly binding to their 3 UTRs [133]. In addition, miR-128-3p and miR-873-5p were identified to make cancer cells more responsive to anti-cancer agents by suppressing ZEB1 expression [162,169] ( Table 5).…”

Section: Mirnas Directly Regulating Emt-related Transcription Factorsmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

View full text Add to dashboard Cite

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

show abstract

“…Hedgehog seinalizazio-bidearen itu-geneen artean, zelula amak autoberriztatzeko baliogarriak diren nanog eta sox2 proteinak daude. Transkripzio-faktore bi horiek ezinbestekoak dira enbrioiaren garapenean zein ehun helduan zelula amen mantentzerako (45). Adibidez, bularreko ehun osasuntsuko zelula ametan zein minbizi-zelula ametan Ptch1 eta Gli geneen gainadierazpena dagoela ikusi da (46).…”

Section: Osagaiz -2016 -1 Aleaunclassified

Minbizi-zelula amak eta seinalizazio-bideak

Arruabarrena¹,

Gallastegui²

2019

Osag

View full text Add to dashboard Cite

LaburpenaAzkenengo urteotan tumoreak azpipopulazio heterogeneoz osatuta daudela iragarri da. Populazio horien artean minbizi-zelula amak edo ingelesez Cancer Stem Cell (CSC) ditugu, tumore berriak sortzeko ahalmena dutenak. Hori dela-eta kartzinogenesiaren erresistentzia terapeutikoarekin erlazionatu dira. Hainbat zelula ama ezagutzen dira: garapen enbrionariokoak, ehun helduetakoak eta minbizi-zelula amak. Guztietan seinalizazio-bide berak aktibatzen dira zelulen beharretara: Wnt, Notch, Hedgehog eta hazkuntza-faktoreak. Egoera normalean, seinalizazioa aktibatzean ligandohartzaileak eta hainbat molekula erreakzio kateatuan nukleora bideratzen dira eta gene ezberdinen transkripzioa eragiten dute; beste gauza batzuen artean, zelulen proliferazioan, desberdintzapenean, heriotzean, mugimenduan edota morfogenesian parte hartzen dute. Seinalizazio-bidea desregulatzen bada, egoera patologiko bat sor daiteke aktibazioaren ondorioz, esaterako minbizia edo endekapenezko gaixotasun bat. Idazki honetan azalduko dugu nola erlazionatzen den seinalizazio-bide horien desregulazioa kartzinogenesiaren sorrerarekin, bereziki minbizi-zelula amen biziraupena sustatuz. Minbiziari aurre egiteko hainbat estrategia elkartu behar dira. Ezagutu behar da nola adierazten diren seinalizazio-bideak tumore bakoitzean eta zein diren horien arteko elkarrekintzak, tratamendu espezifikoagoak diseinatzeko.Gako-hitzak: wnt, notch, shh, gf eta minbizi-zelula ama Abstract It has been recently described that tumors are formed by heterogeneous subpopulations. These populations include cancer stem cells or CSC, which have the potential to generate new tumors, which is why they have been associated with therapeutic resistance to cancer. There exist different stem cells, embryonic and adult and cancer stem cells, where signaling pathways are present; Wnt, Notch, Hh and GF pathways are activated for their cellular needs. When activating the signaling in a natural state, the ligand-receptors and various molecules in a chain reaction reach the nucleus and cause the transcription of different genes; this is related to cell proliferation, differentiation, death, movement or morphogenesis, among other processes. In other cases, if the signaling is dysregulated, it can damage health and create a pathology, such as cancer or degenerative diseases. This paper explains how carcinogenicity is caused by the dysregulation of these signaling pathways, in particular, promoting the survival of CSC. There are several strategies to tackle cancer. Signaling pathways networking need to be studied in each tumor to design treatments that are more specific.

show abstract

Hedgehog Signaling in Cancer: A Prospective Therapeutic Target for Eradicating Cancer Stem Cells

Cited by 149 publications

References 244 publications

Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells

Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Minbizi-zelula amak eta seinalizazio-bideak

Contact Info

Product

Resources

About