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

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 208 ◽  
Author(s):  
Ita Novita Sari ◽  
Lan Thi Hanh Phi ◽  
Nayoung Jun ◽  
Yoseph Toni Wijaya ◽  
Sanghyun Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Hedgehog Signaling ◽  
Molecular Level ◽  
Malignant Tumors ◽  
Cancer Cell Proliferation ◽  
Comprehensive Understanding ◽  
Human Cancers ◽  
Signaling Inhibitors ◽  
Hh Signaling

The Hedgehog (Hh) pathway is a signaling cascade that plays a crucial role in many fundamental processes, including embryonic development and tissue homeostasis. Moreover, emerging evidence has suggested that aberrant activation of Hh is associated with neoplastic transformations, malignant tumors, and drug resistance of a multitude of cancers. At the molecular level, it has been shown that Hh signaling drives the progression of cancers by regulating cancer cell proliferation, malignancy, metastasis, and the expansion of cancer stem cells (CSCs). Thus, a comprehensive understanding of Hh signaling during tumorigenesis and development of chemoresistance is necessary in order to identify potential therapeutic strategies to target various human cancers and their relapse. In this review, we discuss the molecular basis of the Hh signaling pathway and its abnormal activation in several types of human cancers. We also highlight the clinical development of Hh signaling inhibitors for cancer therapy as well as CSC-targeted therapy.

scholarly journals Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

Cell Reports ◽  
2017 ◽  
Vol 21 (10) ◽  
pp. 2813-2828 ◽  
Author(s):  
Joseph L. Regan ◽  
Dirk Schumacher ◽  
Stephanie Staudte ◽  
Andreas Steffen ◽  
Johannes Haybaeck ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Hedgehog Signaling ◽  
Wnt Pathway ◽  
Positive Regulator ◽  
Colon Cancer Stem Cells

scholarly journals Signaling Inhibitors Accelerate the Conversion of mouse iPS Cells into Cancer Stem Cells in the Tumor Microenvironment

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Juan Du ◽  
Yanning Xu ◽  
Saki Sasada ◽  
Aung Ko Ko Oo ◽  
Ghmkin Hassan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Ips Cells ◽  
Signaling Inhibitors

scholarly journals The FDA-Approved Anti-Asthma Medicine Ciclesonide Inhibits Lung Cancer Stem Cells through Hedgehog Signaling-Mediated SOX2 Regulation

2020 ◽  
Vol 21 (3) ◽  
pp. 1014 ◽  
Author(s):  
Hack Sun Choi ◽  
Su-Lim Kim ◽  
Ji-Hyang Kim ◽  
Dong-Sun Lee
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Interfering Rna ◽  
Hedgehog Signaling ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Protein Levels ◽  
Lung Cancer Stem Cells ◽  
Interfering Rna

Ciclesonide is an FDA-approved glucocorticoid (GC) used to treat asthma and allergic rhinitis. However, its effects on cancer and cancer stem cells (CSCs) are unknown. Our study focuses on investigating the inhibitory effect of ciclesonide on lung cancer and CSCs and its underlying mechanism. In this study, we showed that ciclesonide inhibits the proliferation of lung cancer cells and the growth of CSCs. Similar glucocorticoids, such as dexamethasone and prednisone, do not inhibit CSC formation. We show that ciclesonide is important for CSC formation through the Hedgehog signaling pathway. Ciclesonide reduces the protein levels of GL1, GL2, and Smoothened (SMO), and a small interfering RNA (siRNA) targeting SMO inhibits tumorsphere formation. Additionally, ciclesonide reduces the transcript and protein levels of SOX2, and an siRNA targeting SOX2 inhibits tumorsphere formation. To regulate breast CSC formation, ciclesonide regulates GL1, GL2, SMO, and SOX2. Our results unveil a novel mechanism involving Hedgehog signaling and SOX2 regulated by ciclesonide in lung CSCs, and also open up the possibility of targeting Hedgehog signaling and SOX2 to prevent lung CSC formation.

scholarly journals Role of the Hedgehog Signaling Pathway in Regulating the Behavior of Germline Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Shiqin Li ◽  
Meng Wang ◽  
Yanghui Chen ◽  
Wei Wang ◽  
Junying Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Adult Stem Cells ◽  
Reproductive Function ◽  
Future Research ◽  
Germline Stem Cells ◽  
Proliferation And Differentiation ◽  
Hh Signaling

Germline stem cells (GSCs) are adult stem cells that are responsible for the production of gametes and include spermatogonial stem cells (SSCs) and ovarian germline stem cells (OGSCs). GSCs are located in a specialized microenvironment in the gonads called the niche. Many recent studies have demonstrated that multiple signals in the niche jointly regulate the proliferation and differentiation of GSCs, which is of significance for reproductive function. Previous studies have demonstrated that the hedgehog (Hh) signaling pathway participates in the proliferation and differentiation of various stem cells, including GSCs in Drosophila and male mammals. Furthermore, the discovery of mammalian OGSCs challenged the traditional opinion that the number of primary follicles is fixed in postnatal mammals, which is of significance for the reproductive ability of female mammals and the treatment of diseases related to germ cells. Meanwhile, it still remains to be determined whether the Hh signaling pathway participates in the regulation of the behavior of OGSCs. Herein, we review the current research on the role of the Hh signaling pathway in mediating the behavior of GSCs. In addition, some suggestions for future research are proposed.

scholarly journals Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Arif Malik ◽  
Misbah Sultana ◽  
Aamer Qazi ◽  
Mahmood Husain Qazi ◽  
Gulshan Parveen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cells ◽  
Radiation Therapy ◽  
Cancer Stem Cells ◽  
Ionizing Radiation ◽  
Malignant Tumors ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ros Scavenging

Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.

scholarly journals Injury-stimulated Hedgehog signaling promotes regenerative proliferation of Drosophila intestinal stem cells

2015 ◽  
Vol 208 (6) ◽  
pp. 807-819 ◽  
Author(s):  
Aiguo Tian ◽  
Qing Shi ◽  
Alice Jiang ◽  
Shuangxi Li ◽  
Bing Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hedgehog Signaling ◽  
Intestinal Stem Cells ◽  
Homeostatic Proliferation ◽  
Jnk Pathway ◽  
Signaling Axis ◽  
Resident Stem Cells ◽  
Hh Signaling ◽  
Stat Pathway

Many adult tissues are maintained by resident stem cells that elevate their proliferation in response to injury. The regulatory mechanisms underlying regenerative proliferation are still poorly understood. Here we show that injury induces Hedgehog (Hh) signaling in enteroblasts (EBs) to promote intestinal stem cell (ISC) proliferation in Drosophila melanogaster adult midgut. Elevated Hh signaling by patched (ptc) mutations drove ISC proliferation noncell autonomously. Inhibition of Hh signaling in the ISC lineage compromised injury-induced ISC proliferation but had little if any effect on homeostatic proliferation. Hh signaling acted in EBs to regulate the production of Upd2, which activated the JAK–STAT pathway to promote ISC proliferation. Furthermore, we show that Hh signaling is stimulated by DSS through the JNK pathway and that inhibition of Hh signaling in EBs prevented DSS-stimulated ISC proliferation. Hence, our study uncovers a JNK–Hh–JAK–STAT signaling axis in the regulation of regenerative stem cell proliferation.

Clinical Experience With Hedgehog Pathway Inhibitors

2010 ◽  
Vol 28 (36) ◽  
pp. 5321-5326 ◽  
Author(s):  
Jennifer A. Low ◽  
Frederic J. de Sauvage
Keyword(s):  
Stem Cells ◽  
Cell Growth ◽  
Cancer Stem Cells ◽  
Basal Cell Carcinoma ◽  
Myelogenous Leukemia ◽  
Molecule Inhibitor ◽  
Cell Growth And Differentiation ◽  
Hh Signaling ◽  
Tumor Types

The Hedgehog (Hh) signaling pathway is critical for cell growth and differentiation during embryogenesis and early development. While it is mostly quiescent in adults, inappropriate reactivation of the Hh pathway has been shown to be involved in the development of cancer. A number of tumor types rely on overexpression of Hh ligands to activate the pathway in a paracrine manner from the tumor to the surrounding stroma. Alternatively, Hh ligands may act on cancer stem cells in some hematopoietic cancers, such as chronic myelogenous leukemia. However, the role of the Hh pathway is best established in tumors, such as basal cell carcinoma and medulloblastoma, where the pathway is activated via mutations. Understanding the contribution of Hh signaling in these various tumor types will be critical to the development and use of agents targeting this pathway in the clinic. We review here the activity of clinical inhibitors of the Hh pathway, including GDC-0449, a small molecule inhibitor of Smoothened (SMO).

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