Lowered Expression of Tumor Suppressor Candidate MYO1C Stimulates Cell Proliferation, Suppresses Cell Adhesion and Activates AKT

Abstract

Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phosphoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of well-stratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition.

Nuclear myosin 1 activates p21 gene transcription in response to DNA damage through a chromatin-based mechanism

“…3h). This is in agreement with a study in human cancer cells, which showed a higher proliferation rate after Myo1C depletion 22 . To understand this in more detail, we studied the cell cycle distribution of propidium iodide-stained WT and KO cMEFs by flow cytometry (Fig.…”

Myosin isoform expressed in metastatic prostate cancer stimulates cell invasion

“…The result is consistent with the involvement of myosin IC in the free locomotion of retinal and mammary epithelial cells 14 , 15 . In the normal mammary cells, the reduction of free locomotion was connected with a reduction of cell adhesion and spreading, and linked to a loss of contact inhibition 15 . It is likely that the migration of the transformed prostate epithelial cells involves the same mechanisms.…”

“…Myosin IC is involved in the motility of the neuronal growth cones 13 , and recent work established a role for myosin IC in the motility of retinal and mammary epithelial cells in vitro 14 , 15 . The methods employed in these studies did not distinguish between the isoforms, and the cell types were not among the few identified as expressing isoform A 11 .…”

Single-walled and multi-walled carbon nanotubes induce sequence-specific epigenetic alterations in 16 HBE cells

“…Myosin-1C ( MYO1C ), another important gene in the PI3K / AKT signalling pathway, is known to bind with PIP2 and potentially acts as a tumour suppressor [ 52 , 53 ]. MYO1C has also a role in glucose uptake and cell cycle progression.…”