Title:Centrosome Clustering & Chemotherapy
Volume: 23
Issue: 4
Author(s): Farhat Firdous, Hadeeqa Gull Raza, Ghayoor Abbas Chotana, M. Iqbal Choudhary, Amir Faisal and Rahman Shah Zaib Saleem*
Affiliation:
- Department of Chemistry and Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University
of Management Sciences, Lahore, 54792, Pakistan
Keywords:
Cancer, chromosomal instability, multipolarity, chemotherapy, centrosome duplication cycle, centrosome amplification, centrosome clustering, centrosome de-clustering agents.
Abstract: Centrosome abnormalities are the hallmark of cancer. How it affects tumorigenesis is
still a mystery. However, the presence of more than two centrosomes at the onset of mitosis often
leads to chromosomal instability and subsequent tumorigenesis. Unlike normal cells that undergo
repair or apoptosis in response to this instability, cancer cells learn to cope with supernumerary
centrosomes through various mechanisms and survive. Centrosome clustering is the most prevalent
mechanism, allowing the cancer cells to form two daughter cells through a pseudo-bipolar
spindle. Since healthy cells are devoid of the mechanisms involved in clustering, the de-clustering
of centrosomes can be considered a promising approach to selectively eliminate cells with extra
centrosomes. Several proteins such as PARP, KIFC1, Hsp70, Cortical actin, APC/C-CDH1 complex
and Eg5 have been discussed in this review which participate in centrosome clustering, and
the inhibition of these proteins can facilitate in impeding tumor growth specifically by declustering
centrosomes. In this review, we also present the role of the centrosome in the cell cycle, centrosome
amplification, clustering mechanism and reported centrosome de-clustering agents to present
the current state of work in the field.
