Targeting stem cell signaling pathways for drug discovery: advances in the Notch and Wnt pathways

An, Songzhu; Ding, Qiang; Zhang, Jie; Xie, Jingyi; Li, LingSong

doi:10.1007/s11427-014-4665-7

Cited by 19 publications

(12 citation statements)

References 25 publications

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“…CD133 is a cancer stem cell marker and cancer stem cells are widely thought to participate in the chemoresistance of a variety of cancer cells [21,22]. Notch signaling has been demonstrated to regulate cancer stem cell survival [23,24]. Therefore, our findings suggest that miR-34a may exert antichemoresistant effects through inhibiting Notch signaling in cancer stem cells.…”

Section: Discussionmentioning

confidence: 71%

The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms

et al. 2016

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Background: Pancreatic ductaladenocarcinoma (PDAC) exhibits poor prognosis and resistance to chemotherapy. This study was to identify the biomarkers associated with the progression, poor prognosis and chemoresistance of PDAC. Methods: miR-34a and miR-150 levels in the plasma and tissues from PDAC patients were measured by real-time PCR. Xenograft PDAC tumor models were established in mice by inoculation of CD133+ stem cells isolated from PDAC tumors. Protein expression was measured by Western blot. Results: The plasma miR-34a and miR-150 levels were significantly lower in PDAC patients than in patients with benign pancreatic lesions and in healthy subjects. The miR-34a and miR-150 levels in the tumor tissues were significantly lower than in pancreatic tissues with benign lesions. The protein levels of CD133, Notch1, Notch2 and Notch4 receptors in PDAC tumor tissues were significantly higher than in pancreatic tissues with benign lesions. miR-34a injection significantly inhibited the tumor growth of PDAC tumors and sensitized the anticancer effects of 5-fluorouracil (5-FU). miR-34a significantly inhibited Notch1, Notch2 and Notch4 expression in xenograft tumor tissues in vivo and BxPC-3 cells in vitro. miR-34a and miR-150 significantly induced apoptosis and inhibited proliferation, invasion and migration in BxPC-3 cells. miR-34a, but not miR-150, significantly sensitized the anticancer effect of 5-FU in BxPC-3 cells in vitro. Conclusion: A loss of expression of miR-34a, but not of miR-150, is associated with disease progression and poor prognosis in PDAC patients, and may be involved in the chemoresistance of PDAC cells.

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Section: Discussionmentioning

confidence: 71%

The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms

et al. 2016

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“…BMP4 is an important regulator of neural development. During the development of the nervous system, there is 'crosstalk' between the BMP and Wnt signaling pathways ( 28 – 30 ). Therefore, the current study measured the expression levels of Ngn1 and BMP4 in NSCs exposed to HIBD brain tissue homogenate by semiquantitative RT-PCR and western blotting.…”

Section: Discussionmentioning

confidence: 99%

Impact of siRNA targeting of β-catenin on differentiation of rat neural stem cells and gene expression of Ngn1 and BMP4 following in vitro hypoxic-ischemic brain damage

Zhang

Zhu

Luo

et al. 2016

Molecular Medicine Reports

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The aim of the present study was to investigate the possible damage-repair mechanisms of neural stem cells (NSCs) following hypoxic-ischemic brain damage (HIBD). NSCs obtained from Sprague Dawley rats were treated with tissue homogenate from normal or HIBD tissue, and β-catenin expression was silenced using siRNA. The differentiation of NSCs was observed by immunofluorescence, and semiquantitative reverse transcription-polymerase chain reaction and western blot analysis were applied to detect the mRNA and protein expression levels of Ngn1 and BMP4 in the NSCs. Compared with control NSCs, culture with brain tissue homogenate significantly increased the differentiation of NSCs into neurons and oligodendrocytes (P<0.05), whereas differentiation into astrocytes was significantly reduced (P<0.05). Compared with negative control-transfected cells, knockdown of β-catenin expression significantly decreased the differentiation of NSCs into neurons and oligodendrocytes (P<0.01), whereas the percentage of NSCs differentiated into astrocytes was significantly increased (P<0.01). Compared with control NSCs, the mRNA and protein expression levels of Ngn1 were significantly increased (P<0.01) and BMP4 levels were significantly reduced (P<0.01) by exposure of the cells to brain tissue homogenate. Compared with the negative control plasmid-transfected NSCs, the levels of Ngn1 mRNA and protein were significantly reduced by β-catenin siRNA (P<0.01), whereas BMP4 levels were significantly increased (P<0.01). In summary, the damaged brain tissues in HIBD may promote NSCs to differentiate into neurons for self-repair processes. β-Catenin, BMP4 and Ngn1 may be important for the coordination of NSC proliferation and differentiation following HIBD.

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“…The main signaling pathways involved include Hedgehog, Wnt, Notch, BMP, Bmi, PI3K/Akt, etc. [ 139 ]. Many lines of evidence support the idea that SHH signaling is important in maintaining cancer stem cell in various cancers [ 12 , 140 , 141 , 142 ].…”

Section: Using Smo Antagonists To Inhibit Cancer Stem Cellsmentioning

confidence: 99%

The Role of Smoothened in Cancer

Jeng

Sheen

Leu³

et al. 2020

IJMS

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Smoothened (SMO) belongs to the Hedgehog (HH) signaling pathway, which regulates cell growth, migration, invasion and stem cells in cancer. The HH signaling pathway includes both canonical and noncanonical pathways. The canonical HH pathway functions through major HH molecules such as HH ligands, PTCH, SMO and GLI, whereas the noncanonical HH pathway involves the activation of SMO or GLI through other pathways. The role of SMO has been discussed in different types of cancer, including breast, liver, pancreatic and colon cancers. SMO expression correlates with tumor size, invasiveness, metastasis and recurrence. In addition, SMO inhibitors can suppress cancer formation, reduce the proliferation of cancer cells, trigger apoptosis and suppress cancer stem cell activity. A better understanding of the role of SMO in cancer could contribute to the development of novel therapeutic approaches.

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Targeting stem cell signaling pathways for drug discovery: advances in the Notch and Wnt pathways

Cited by 19 publications

References 25 publications

The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms

The Clinical Significance of miR-34a in Pancreatic Ductal Carcinoma and Associated Molecular and Cellular Mechanisms

Impact of siRNA targeting of β-catenin on differentiation of rat neural stem cells and gene expression of Ngn1 and BMP4 following in vitro hypoxic-ischemic brain damage

The Role of Smoothened in Cancer

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