RITA, the RBP-J interacting and tubulin associated protein, has been recently identified as a crucial modulator of the Notch
signaling pathway and as a novel regulator of microtubule (MT) dynamics. Its expression
levels are well correlated with the differentiation status of primary human hepatocellular
carcinoma (HCC) cells. Moreover, elevated levels of RITA expression are correlated
with unfavorable clinical outcome in anal carcinoma treated with concomitant chemoradiotherapy.
We asked if RITA is involved in the migration and invasion potential of breast cancer
cells.
Cellular and molecular biological methods including immunofluorescence staining and
living cell microscopy were used to study the impact of RITA in cancer cells, in particular,
in highly invasive MDA-MB-231, low malignant MCF-7 and cervical carcinoma HeLa cells.
We show here that depletion of RITA reduces the migration, whereas overexpression
of RITA enhances this ability in breast cancer cells MCF-7 and MDA-MB-231. Tracking
individual single cells using time-lapse microscopy reveals that the level of RITA
is correlated with the motility of breast cancer cells. The acetylation of α-tubulin
within MTs is increased in breast cancer cells depleted of RITA. Suppression of RITA
increases stability of focal adhesions indicated by elevated signals of active phosphorylated
focal adhesion kinase.
This work indicates a novel role for RITA in the regulation of cancer cell migration
by modulating the dynamics of focal adhesion proteins, probably through the modulation
of tubulin, which leads to alteration in MT dynamics. The data suggest that RITA could
influence the migratory and invasive behavior of breast cancer cells.
