Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy

Wu, Chen; Zhu, Xiaojie; Liu, Weizhen; Ruan, Tuo; Tao, Kaixiong

doi:10.2147/ott.s139639

Cited by 69 publications

(50 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the Notch and Hedgehog pathways have been shown in several studies to play a role in CRC development and progression, data are still contradictory and unclear (57). In our study, activation of the two examined pathways, as this is indicated by IHC overexpression of their components, did not result in significant associations in terms of outcome in early-stage CRC patients, with the exception of Notch3.…”

Section: Resultscontrasting

confidence: 63%

Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer

Rallis

Κoletsa

Saridaki³

et al. 2019

Anticancer Res

View full text Add to dashboard Cite

Background/Aim: Early-stage colorectal cancer (CRC) carries a wide range of survival probabilities. Novel biomarkers in this setting are eagerly awaited. Cancer stem cells (CSCs) are considered one of the reasons for treatment failure. This study sought to determine whether activation of pathways governing the function of CSC's could correlate with treatment outcomes. Materials and Methods: Tumor specimens from 325 patients were analyzed with immunohistochemistry (IHC) for Hedgehog and Notch pathway activation and results were correlated with prognosis. Results: Positive Notch3 protein expression was an unfavorable prognostic factor for disease-free survival (DFS) and overall survival (OS) (HR=2.43, p=0.024 and HR=2.56, p=0.028, respectively). Activation of the Shh pathway showed univariately longer DFS (HR=0.49, p=0.032). Possible crosstalk between the two pathways was indicated. No further associations between pathway activation and outcome were evident. Conclusion: Apart from Notch 3, activation of the pathways, as indicated by IHC expression of their components, did not result in differences in terms of DFS or OS.

show abstract

Section: Resultscontrasting

confidence: 63%

Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer

Rallis

Κoletsa

Saridaki³

et al. 2019

Anticancer Res

View full text Add to dashboard Cite

show abstract

“…Components of the hedgehog signaling pathway, such as SMO, Gli1, and Gli2, are deregulated in various cancers, and their expression levels are correlate with tumor progression and metastasis [14,22,29,30]. Aberrant activation of the hedgehog signaling pathway may promote colon cancer growth, recurrence, metastasis and stem cell survival and expansion [31,32]. Our study showed that when BEX2 was knocked out, the hedgehog signaling pathway could be activated.…”

Section: Discussionmentioning

confidence: 79%

Silencing of brain-expressed X-linked 2 (BEX2) promotes colorectal cancer metastasis through the Hedgehog signaling pathway

Tan¹,

Hu²,

Xiao³

et al. 2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

The incidence of colorectal cancer is increasing, and cancer metastasis is one of the major causes of poor outcomes. BEX2 has been reported to be involved in tumor development in several types of cancer, but its role in metastatic colorectal cancer remains largely undefined. Herein, we demonstrated that BEX2 knockout resulted in enhanced migratory and metastatic potential in colorectal cancer cells both in vitro and in vivo, and re-expression of BEX2 in knockout cells could reverse the enhanced migratory capacity. RNA-Seq results indicated that the hedgehog signaling pathway was activated after BEX2 knockout; moreover, the hedgehog signaling inhibitors, GANT61 and GDC-0449 could reverse the migratory enhancement of BEX2-/-colorectal cancer cells. We also demonstrated that the nuclear translocation of Zic2 after BEX2 silencing could activate the hedgehog signaling pathway, while Zic2 knockdown abrogated the migratory enhancement of BEX2-/-cells and inhibited the hedgehog signaling pathway. In summary, our findings suggest that BEX2 negatively modulates the hedgehog signaling pathway by retaining Zic2 in the cytoplasm in colorectal cancer cells, thereby inhibiting migration and metastasis of colorectal cancer cells.

show abstract

“…Approximately 90% of colorectal cancer-related mortality is caused by tumor distant metastases [ 28 ]. Suppression of tumor invasion can effectively inhibit tumor cell spread and infiltration into distant organs.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic Activity of Wrap53 in Human Colorectal Cancer In Vitro and in Nude Mouse Xenografts

et al. 2018

View full text Add to dashboard Cite

BackgroundWD40-encoding RNA antisense to p53 (Wrap53) has been implicated in cancer development. However, the role of Wrap53 remains unknown in colorectal cancer. The aim of this study was to elucidate the function of Wrap53 in colorectal cancer tumorigenesis and development.Material/MethodsThis study analyzed Wrap53 expression in colorectal cancer tissue specimens using The Cancer Genome Atlas data and tumor cell lines and assessed the effects of Wrap53 knockdown on regulation of cancer cell malignant phenotypes in vitro and in nude mouse xenografts.ResultsWrap53 expression was upregulated in colorectal cancer tissue specimens and cell lines. Knockdown of Wrap53 expression induced colorectal cancer cell line apoptosis and cell cycle arrest in the G1 phase, but reduced tumor cell line proliferation and invasion in vitro. Knockdown of Wrap53 in a nude mouse xenograft assay inhibited tumor cell line xenograft formation and growth.ConclusionsWrap53 is likely a potential oncogene or possesses oncogenic activity in colorectal cancer, promoting colorectal tumorigenesis. Targeting Wrap53 expression may represent a novel strategy for the control of colorectal cancer.

show abstract

Hedgehog signaling pathway in colorectal cancer: function, mechanism, and therapy

Cited by 69 publications

References 113 publications

Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer

Association of Notch and Hedgehog Pathway Activation With Prognosis in Early-stage Colorectal Cancer

Silencing of brain-expressed X-linked 2 (BEX2) promotes colorectal cancer metastasis through the Hedgehog signaling pathway

Oncogenic Activity of Wrap53 in Human Colorectal Cancer In Vitro and in Nude Mouse Xenografts

Contact Info

Product

Resources

About