Fig. 5
From: The role of kinesin family members in hepatobiliary carcinomas: from bench to bedside
The roles of the kinesin-12, 13, 14 family members in HCC. (A) Kinesin-12 family: KIF15 interacts with proteasome 26 S subunit, non-ATPase 12 (PSMD12) and is stimulated by it. And the regulative impacts of KIF15 on HCC cells growth, proliferation, migration, and chemo-resistance have been linked to the MEK/ERK signaling. Furthermore, KIF15 also eliminates intracellular reactive oxygen species (ROS) accumulation and facilitates tumor stem cell phenotype by interacting with phosphoglycerate dehydrogenase (PHGDH) and stabilizing its expression via inhibiting proteasomal degradation. (B) Kinesin-13 family: KIF2C mediated cross-talk between WNT/β-catenin and mTORC1 signaling: WNT/β-catenin signaling caused transcriptional up-regulation of KIF2C when TCF4 bound to the KIF2C promoter. Subsequently, KIF2C interacted with TBC1D7 causing destabilization of TSC1/2 and reduced the anti-oncogenic effect of TSC2 on mTORC1 signaling transduction, finally promoted tumor development. Moreover, the pro-tumor impacts of KIF2C might also be attributed to its latent regulatory function in the Ras/MAPK and MEK/ERK signaling axes. Another family member KIF2A, negatively regulated by miR-424-5p, has also been demonstrated to facilitate malignant progression via the Notch 1 signaling, in which KIF2A interacts with Notch 1 and positively regulates its expression. (C) Kinesin-14 family: Similar to KIF2C, KIFC1 can also be transcriptionally up-regulated by TCF4, and aberrant activation of KIFC1 facilitates HCC progression through enhancing the transcriptional activity of High Mobility Group AT-Hook 1 (HMGA1), which regulates several cancer-related genes transcription (including STAT3, MMP2, E-cadherin, Vimentin, Twist1) by binding to their corresponding promoter regions. Besides, KIFC1 also participates in the stimulation of PI3K/Akt signaling via up-regulating the expression of gankyrin. Similarly, miR-532-3p plays an inhibitory role in this process by directly suppressing KIFC1 expression. As for KIFC3, it has also been demonstrated to stimulate HCC development through activating PI3K/Akt/mTOR signaling pathway