KIFC1: a promising chemotherapy target for cancer treatment?

Yu-Xi Xiao,Wan-Xi Yang

doi:10.18632/oncotarget.8799

Abstract

The kinesin motor KIFC1 has been suggested as a potential chemotherapy target due to its critical role in clustering of the multiple centrosomes found in cancer cells. In this regard, KIFC1 seems to be non-essential in normal somatic cells which usually possess only two centrosomes. Moreover, KIFC1 is also found to initiatively drive tumor malignancy and metastasis by stabilizing a certain degree of genetic instability, delaying cell cycle and protecting cancer cell surviving signals. However, that KIFC1 also plays roles in other specific cell types complicates the question of whether it is a promising chemotherapy target for cancer treatment. For example, KIFC1 is found functionally significant in vesicular and organelle trafficking, spermiogenesis, oocyte development, embryo gestation and double-strand DNA transportation. In this review we summarize a recent collection of information so as to provide a generalized picture of ideas and mechanisms against and in favor of KIFC1 as a chemotherapy target. And we also drew the conclusion that KIFC1 is a promising chemotherapy target for some types of cancers, because the side-effects of inhibiting KIFC1 mentioned in this review are theoretically easy to avoid, while KIFC1 is functionally indispensable during mitosis and malignancy of multi-centrosome cancer cells. Further investigations of how KIFC1 is regulated throughout the mitosis in cancer cells are needed for the understanding of the pathways where KIFC1 is involved and for further exploitation of indirect KIFC1 inhibitors.

Highlights

Kinesin-14 family proteins are C-terminal kinesins with special minus end motility on microtubules
What should be emphasized is that research on the endocytic vesicle trafficking role of KIFC1, discussed as a potential barrier towards the use of KIFC1 inhibitors, has included evidence from cancer cell lines
Since we don’t know whether endocytic vesicle trafficking is relevant to unique metabolism processes of cancer cells and whether knockdown of KIFC1 in those cell lines causes higher death rates compared to that of knockdown of proper control cells, those experiments could be considered as evidence for either side based on different arguments

Summary

Introduction

Kinesin-14 family proteins are C-terminal kinesins with special minus end motility on microtubules. This suggests that ch-TOG can limit the binding between microtubules and KIFC1, so as to decrease the functional activity of KIFC1 as a regulator in human cancer cells (Figure 2B). Besides centrosome clustering activity and cell cycle alteration ability, by protecting cancer cell surviving signals, KIFC1 further enhances tumor malignancy (Figure 1).

Results

Conclusion