KIF11 and Associated Diseases
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Overview of KIF11
In humans, kinesin-like protein KIF11 (KIF11, also known as Kinesin Family Member 11 or Kinesin-5) is a molecular motor protein encoded by the gene KIF11. KIF11 belongs to the kinesin superfamily, which is nanomotors and has the ability to move along microtubule tracks in the cell by converting chemical energy into mechanical force. KIF11 and other members of the kinesin superfamily are involved in the spindle dynamics and are essential for mitosis. During mitosis, KIF11 can position the chromosome, separate the centrosome, and establish a bipolar spindle.
Fig.1 The structure of KIF11. (Wikipedia)
KIF11 in Disease
Diseases associated with KIF11 include cancers such as colorectal cancer and breast cancer, and microcephaly with or without chorioretinopathy, lymphedema, or mental retardation.
- Colorectal cancer
KIF11 can serve as a potential oncogene in colorectal cancer (CRC). KIF11 plays a key role in the establishment of the bipolar spindle and is upregulated in several cancer types including CRC. In clinical samples of CRC, the expression of KIF11 is upregulated, which is related to the advanced clinical stage and enhanced vessel invasion. Oxaliplatin, as a chemotherapy drug, is frequently administered to CRC patients. Knockdown of KIF11 in CRC cells leads to tumor growth arrest and increases the cell sensitivity to oxaliplatin, where enhanced DNA damage and cell apoptosis can be observed. Thus, KIF11 can be regarded as a marker to assess the oxaliplatin sensitivity of CRC.
- Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation
KIF11 mutations are associated with microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR). MCLMR is an inherited disorder with typical characteristics such as microcephaly and abnormal facial. According to whole-exome sequencing, a new heterozygous mutation in exon 20 of KIF11 is identified. This variant influences the normal splicing of KIF11 pre-mRNA, resulting in the c.2815_2922 deletion of exon 20. The KIF11 variant will induce the expression of a shortened KIF11 protein with an incomplete C-terminal domain. In summary, the new variant expands the correlation between KIF11 and MCLMR.
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References
- Zhou, Y.; et al. KIF11 is upregulated in colorectal cancer and silencing of it impairs tumor growth and sensitizes colorectal cancer cells to oxaliplatin via p53/GSK3β signaling. J. Cancer. 2021, 12: 3741–3753.
- Guo, Z.; et al. A Novel Variant of the KIF11 Gene, c.2922G>T, Is Associated with Microcephaly by Affecting RNA Splicing. Dev Neurosci. 2022, 44: 113–120.
