Cancer Stem Cells Equipped with Powerful Hedgehog Signaling and Better Epigenetic Memory: Avenues to Look for Cancer Therapeutics

2019 ◽  
Vol 19 (11) ◽  
pp. 877-884 ◽  
Author(s):  
Ishita Tandon ◽  
Asawari Waghmode ◽  
Nilesh Kumar Sharma
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Cancer Therapeutics ◽  
Complex Nature ◽  
Epigenetic Memory ◽  
Therapeutic Approaches ◽  
Shh Signaling ◽  
Memory Power

Complex nature of the tumor is depicted at the cellular landscape by showing heterogeneity in the presence of cancer cells, cancer-associated stromal cells, mesenchymal stem cells and cancer stem cells (CSCs). One of the plausible views in cancer formation is suggested as the theory of cancer CSCs that is known as a source of initiation of tumorigenesis. In essence, these powerful CSCs are equipped with high Sonic Hedgehog (SHH) signaling and epigenetic memory power that support various tumor hallmarks. Truly, nature justifies its intent by limiting these stem cells with a potential to turn into CSCs and in turn suppressing the high risk of humans and other organisms. In short, this mini-review addresses the contribution of SHH signaling to allow reprogramming of epigenetic memory within CSCs that support tumor hallmarks. Besides, this paper explores therapeutic approaches to mitigate SHH signaling that may lead to a blockade of the pro-tumor potential of CSCs.

scholarly journals Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Polyhomeotic Homolog 3 and Sonic Hedgehog Signaling Pathways

2019 ◽  
Author(s):  
FanPing Wang ◽  
Jiateng Zhong ◽  
Shanshan Wang ◽  
Caijuan Qiao ◽  
Xiangyang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Western Blot ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Self Renewal ◽  
Shh Signaling ◽  
Lung Cancer Stem Cells

Abstract Background: Sulforaphane (SFN), an active compound in cruciferous vegetables has been characterized for its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. Methods: Lung cancer stem cells (CD133-positive cells) were isolated by MACs and then measured by flow cytometry. The ability of cell proliferation was assessed by MTT assays and tumorsphere formation assays. The expressions of Sonic Hedgehog (Shh), Smoothened (Smo), Gli1 and Human Polyhomeotic Homolog 3 (PHC3) in cells were measured by quantitative reverse transcription polymerase chain reaction (qPCR) and western blot assays. The expression of transcription factor SOX2 in lung cancer stem cells was also determined by western blot assay. Shh was knocked down by siRNA to further study the role of SFN and Shh signaling pathways in lung cancer. Results: SFN inhibited the proliferation of lung cancer cells and lung cancer stem cells simultaneously. Meanwhile, we observed that Sonic Hedgehog (SHH) signaling pathway, SOX2 and Polyhomeotic Homolog 3 (PHC3) were highly activated in lung cancer stem cells. Knock-down of Shh led to reduced H460 and A549 cells proliferation. Furthermore, we observed that SFN inhibited the activity of PHC3 and SHH signaling pathways in the lung cancer stem cells. In addition, SFN combined with Knock-down of Shh gene showed a greater effect on the proliferation of lung cancer cells. Conclusion: SFN is an effective new drug which can inhibit proliferation of lung cancer stem cells through the modulation of PHC3 and SHH signaling pathways. It provides a novel target for improving therapeutic efficacy for lung cancer stem cells.

scholarly journals Sulforaphane inhibits self-renewal of lung cancer stem cells through the modulation of sonic Hedgehog signaling pathway and polyhomeotic homolog 3

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fanping Wang ◽  
Yanwei Sun ◽  
Xiaoyu Huang ◽  
Caijuan Qiao ◽  
Wenrui Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Lung Cancer Cells ◽  
Sonic Hedgehog Signaling ◽  
Self Renewal ◽  
Lung Cancer Stem Cells

AbstractSulforaphane (SFN), an active compound in cruciferous vegetables, has been characterized by its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. CD133+ cells were isolated with MACs from lung cancer A549 and H460 cells. In this study, we found that SFN inhibited the proliferation of lung cancer cells and self-renewal of lung cancer stem cells simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in CD133+ lung cancer cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of CD133+ lung cancer cells, and decreased the protein expression of PHC3 in CD133+ lung cancer cells. Knock-down of PHC3 also affected the proliferation and decreased the Shh expression level in CD133+ lung cancer cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in CD133+ lung cancer cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-Shh and siRNA-PHC3 cells was weaker than that on the proliferation of siRNA-control cells. Sonic Hedgehog signaling pathway might undergo a cross-talk with PHC3 in self-renewal of lung cancer stem cells. SFN might be an effective new drug which could inhibit self-renewal of lung cancer stem cells through the modulation of Sonic Hedgehog signaling pathways and PHC3. This study could provide a novel way to improve therapeutic efficacy for lung cancer stem cells.

Role of Organ Specific Cancer Stem Cells in Organ Specific Cancer Progression

2020 ◽  
Vol 6 (2) ◽  
pp. 21
Author(s):  
Muhammad Ali ◽  
Fatima Ali ◽  
Nadia Wajid
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Cancer Therapeutics ◽  
Therapeutic Approaches ◽  
Specific Cancer ◽  
Organ Specific

Since the cancer stem cells (CSC) have been identified in 1997 by Bonnet and Dick, more than 100,000 papers have been published on the CSC. Huge research on cancer stem cells helped the scientists to rethink about the cancer therapeutics as classic way of chemotherapy is ineffective because chemotherapy failed to kill these cells, the only reason of cancer relapse. The cancer theory of stem cells is one of the most trending theory in stem cells and cancer biology focusing on the understanding of biology of cancer cells for an enhanced and improved therapeutic approaches should be applied to cure the cancer. This mini-review is a short overview on the role of organ specific cancer stem cells in the organ specific cancer progression.

scholarly journals Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Sonic Hedgehog Signaling Pathway and Polyhomeotic Homolog3

2021 ◽  
Author(s):  
FanPing Wang ◽  
Yanwei Sun ◽  
Xiaoyu Huang ◽  
Caijuan Qiao ◽  
Wenrui Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Sonic Hedgehog ◽  
Self Renewal ◽  
Shh Signaling ◽  
Lung Cancer Stem Cells

Abstract Sulforaphane (SFN), an active compound in cruciferous vegetables has been characterized for its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells (CSCs). CD133-positive lung cancer cells were isolated by MACs from lung cancer A549 and H460 cells. And then, the expression of CD133 was measured by flow cytometry assays (FACS). The ability of cell proliferation was assessed by MTT assays and tumorsphere formation assays. The mRNA expression of Sonic Hedgehog (Shh), Smoothened (Smo), Gli1 and Human Polyhomeotic Homolog 3 (PHC3) was measured by quantitative reverse transcription polymerase chain reaction (QPCR). And the protein expression of Shh, Smo, Gli1 and PHC3 was determined by western blotting. Shh was knocked down by siRNA to further study the role of Shh signaling pathways in lung CSCs. SFN inhibited the proliferation of lung cancer cells and lung CSCs simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in A549 /CD133+ and H460 /CD133+ cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of A549/ CD133+ and H460/ CD133+ cells, and decreased the protein expression of PHC3 in A549/ CD133+ and H460/ CD133+ cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in A549/ CD133+ and H460/ CD133+ cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-shh cells is weaker than that of siRNA-control cells. SFN is an effective new drug which can inhibit proliferation of lung CSCs through the modulation of PHC3 and SHH signaling pathways. It provides a novel target for improving therapeutic efficacy for lung CSCs.

Genistein inhibits nasopharyngeal cancer stem cells through sonic hedgehog signaling

2019 ◽  
Vol 33 (10) ◽  
pp. 2783-2791 ◽  
Author(s):  
Qi Zhang ◽  
Wan‐Shuang Cao ◽  
Xue‐Qi Wang ◽  
Min Zhang ◽  
Xiao‐Min Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Nasopharyngeal Cancer ◽  
Sonic Hedgehog Signaling

scholarly journals TP53 promotes lineage commitment of human embryonic stem cells through ciliogenesis and sonic hedgehog signaling

2021 ◽  
Author(s):  
Sushama Sivakumar ◽  
Shutao Qi ◽  
Ningyan Cheng ◽  
Adwait amod sathe ◽  
Mohammed Kanchwala ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Sonic Hedgehog ◽  
Human Embryonic Stem Cells ◽  
Hedgehog Signaling ◽  
Neural Progenitor Cells ◽  
Embryonic Stem ◽  
Low Grade ◽  
Shh Signaling

Aneuploidy, defective differentiation, and inactivation of the tumor suppressor TP53 all occur frequently during tumorigenesis. Here, we probe the potential links among these cancer traits by inactivating TP53 in human embryonic stem cells (hESCs). TP53 knockout hESCs exhibit increased proliferation rates, mitotic errors, and low-grade structural aneuploidy; produce poorly differentiated immature teratomas in mice; and fail to differentiate into neural progenitor cells (NPC) in vitro. Genome-wide CRISPR screen reveals requirements of ciliogenesis and sonic hedgehog (Shh) pathways for hESC differentiation into NPCs. TP53 deletion causes abnormal ciliogenesis in neural rosettes. In addition to restraining cell proliferation through CDKN1A, TP53 activates the transcription of BBS9, which encodes a ciliogenesis regulator required for proper Shh signaling and NPC formation. This developmentally regulated transcriptional program of TP53 promotes ciliogenesis, restrains Shh signaling, and commits hESCs to neural lineages.

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