Spatial and single-cell explorations uncover prognostic significance and immunological functions of mitochondrial calcium uniporter in breast cancer

  • 0Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, 813, Taiwan.

|

|

Summary

This summary is machine-generated.

The mitochondrial calcium uniporter (MCU) is a novel biomarker for breast cancer (BRCA), impacting prognosis and immune cell infiltration. MCU alterations suggest potential for precision medicine and drug screening in BRCA.

Area Of Science

  • Biochemistry and Molecular Biology
  • Oncology
  • Immunology

Background

  • Mitochondrial calcium uniporter (MCU) regulates cellular calcium homeostasis, vital for energy and cell death.
  • Its role in the breast cancer (BRCA) tumor microenvironment and clinical pathology is largely unknown.
  • Investigating MCU offers potential for advancements in BRCA diagnostics, prognostics, and precision oncology.

Purpose Of The Study

  • To identify MCU as a diagnostic and prognostic biomarker in breast cancer (BRCA).
  • To explore the association between MCU expression, the tumor immune microenvironment, and clinical outcomes in BRCA.
  • To investigate the therapeutic implications of MCU alterations in BRCA.

Main Methods

  • Multi-omics analysis utilizing public datasets (GEO, TCGA).
  • Spatial transcriptomics and single-cell RNA-sequencing for spatial and cellular correlation analysis.
  • Immunohistochemistry validation on BRCA patient samples.

Main Results

  • MCU identified as an independent diagnostic biomarker for BRCA, linked to advanced stage and poor survival.
  • MCU expression correlates with immune gene expression, tumor stage, and infiltrating immune cells, notably CD8+ T cells.
  • Pharmacogenomic analysis suggests MCU inactivation enhances sensitivity to certain drugs in BRCA cell lines.

Conclusions

  • MCU alterations are implicated in BRCA progression, offering new diagnostic and prognostic insights.
  • MCU plays a significant role in the BRCA tumor immune microenvironment and cell cycle.
  • MCU represents a potential target for precision medicine and drug development in BRCA.

Related Concept Videos

mTOR Signaling and Cancer Progression 03:03

3.8K

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...

Electron Transport Chain: Complex I and II 01:46

13.1K

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...

Translocation of Proteins into the Mitochondria 01:19

3.1K

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...

Mitogens and the Cell Cycle 02:38

6.5K

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...

Mitochondrial Precursor Proteins 01:39

2.6K

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...

Mitochondrial Protein Sorting 01:39

4.3K

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...