Notch1 regulates the functional contribution of RhoC to cervical carcinoma progression.
BACKGROUND
The role of Notch signalling in human epithelial cancers is of immense interest. In this study, we examine the interplay between Notch signalling and RhoC, a well-established molecular factor in metastasis. By linking the function of Notch and RhoC, we further strengthen the notion that there is a pro-oncogenic role of Notch signalling in human cervical cancers.


METHODS
RhoC protein expression in cervical carcinoma cell lines was assessed by western blotting. Using CaSki and SiHa cells (cervical carcinoma cells lines), we show that RhoC contributes to wound healing, invasion and migration, anoikis resistance, colony formation, in vitro tube formation and tumour formation. Immunohistochemical studies were carried out to assess the co-expression of RhoC, pAkt and Notch1 in clinical sections.


RESULTS
An assessment of the changes associated with epithelial-to-mesenchymal transition (EMT) shows that both Notch1 and RhoC have similar phenotypic contribution to EMT. Rho activity assessment on Notch1 inhibition with DAPT shows decreased RhoC activity. We further show that constitutively active RhoC rescues the phenotypic effect of Notch1 inactivation, and a comparison of Notch1 with RhoC expression shows an overlap between the two proteins in the same areas of the tissue.


CONCLUSIONS
This study has provided evidence to suggest that RhoC is an effector of Notch1 in cervical carcinoma.
Srivastava
S
S
National Centre for Biological Sciences, TIFR, Bangalore, Karnataka, India. sweta@ncbs.res.in
Ramdass
B
B
Nagarajan
S
S
Rehman
M
M
Mukherjee
G
G
Krishna
S
S
D000818:Animals; D023102:Anoikis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D054338:Cell Transdifferentiation; D018450:Disease Progression; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D000075024:rhoC GTP-Binding Protein
C497761:NOTCH1 protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein