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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression
S Srivastava1, B Ramdass, S Nagarajan
1National Centre for Biological Sciences, TIFR, Bangalore, Karnataka, India. sweta@ncbs.res.in
British Journal of Cancer
|December 3, 2009
Summary
Notch signalling and RhoC protein play pro-oncogenic roles in cervical cancers. This study shows RhoC acts as an effector of Notch1, impacting metastasis and tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Notch signalling is implicated in human epithelial cancers.
- RhoC is a known factor in cancer metastasis.
- The interplay between Notch and RhoC in cervical cancer warrants investigation.
Purpose of the Study:
- To investigate the functional relationship between Notch signalling and RhoC in cervical cancer.
- To determine if Notch signalling influences RhoC activity.
- To establish RhoC as a downstream effector of Notch1 in cervical carcinoma.
Main Methods:
- Western blotting to assess RhoC expression in cervical cancer cell lines.
- Functional assays (wound healing, invasion, migration, anoikis resistance, colony formation, in vitro tube formation, tumor formation) using CaSki and SiHa cells.
- Immunohistochemistry to evaluate co-expression of RhoC, pAkt, and Notch1 in clinical samples.
Main Results:
- Notch1 and RhoC exhibit similar contributions to epithelial-to-mesenchymal transition (EMT).
- Inhibition of Notch1 using DAPT decreased RhoC activity.
- Constitutively active RhoC reversed the phenotypic effects of Notch1 inactivation.
- Overlapping expression patterns of Notch1 and RhoC were observed in tumor tissues.
Conclusions:
- RhoC functions as an effector of Notch1 in cervical carcinoma.
- This study supports a pro-oncogenic role for Notch signalling in cervical cancers.
- The findings highlight a potential therapeutic target by linking Notch1 and RhoC pathways.
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