Related Experiment Video

Updated: Mar 18, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

896

Mps1 kinase regulates tumor cell viability via its novel role in mitochondria

X Zhang1, Y Ling2, Y Guo1,3

  • 1State Key Laboratory for Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.

Cell Death & Disease
|July 8, 2016
PubMed

Insights

Targeting monopolar spindle 1 (Mps1) kinase in colon cancer reveals a novel mitochondrial role essential for cell survival beyond its known function in the spindle assembly checkpoint (SAC). Inhibiting Mps1

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Monopolar spindle 1 (Mps1) kinase is a validated target in cancer therapy, primarily known for its role in the spindle assembly checkpoint (SAC).
  • The precise mechanisms by which Mps1 influences cancer cell viability, particularly in colon cancer, remain incompletely understood.
  • Existing research suggests Mps1's role in cell viability may extend beyond its canonical function in the SAC.

Purpose of the Study:

  • To investigate the role of elevated Mps1 levels in colon cancer development and survival.
  • To elucidate the non-SAC-dependent functions of Mps1 critical for cancer cell viability.
  • To explore Mps1's novel interactions and functions, particularly in mitochondria, for therapeutic targeting.

Main Methods:

  • Utilized aneuploid colon cancer cell lines to assess Mps1 requirements for cell survival versus SAC maintenance.
  • Developed and applied a single-cycle inhibition strategy to selectively target Mps1 function during mitosis.
  • Investigated Mps1's interaction with voltage-dependent anion channel 1 (VDAC1) and its impact on mitochondrial function and cell death.

Main Results:

  • Mps1 levels required for cell survival significantly exceed those for SAC maintenance in aneuploid colon cancer cells.
  • Short-term Mps1 inhibition during mitosis is sufficient to induce cell death, independent of cytokinesis.
  • Mps1 interacts with VDAC1 in mitochondria, and this interaction is crucial for cell viability; its disruption leads to cytochrome c release and cell death.

Conclusions:

  • Mps1 possesses critical functions beyond the SAC that are essential for colon cancer cell viability.
  • Targeting Mps1's novel mitochondrial localization and function offers a promising therapeutic strategy for colon cancer.
  • Inhibition of mitochondrial Mps1 is sufficient to induce tumor cell death, suggesting a new therapeutic avenue.

More Related Videos

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima09:13

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima

Published on: August 12, 2018

15.9K
Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

18.7K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.8K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.7K