Key regulator PNPLA8 drives phospholipid reprogramming induced proliferation and migration in triple-negative breast

Zheqiong Tan1,2, Pragney Deme3, Keerti Boyapati1

  • 1Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PubMed
Abstract

Insights

Researchers identified patatin-like phospholipase domain-containing lipase 8 (PNPLA8) as a key driver in triple-negative breast cancer (TNBC). Targeting PNPLA8 could offer new therapeutic strategies for this aggressive cancer subtype.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype with poor patient outcomes.
  • Current treatments including surgery and chemotherapy are often insufficient for TNBC.
  • Novel molecular targets are crucial for improving TNBC therapeutic options.

Purpose of the Study:

  • To identify novel therapeutic targets for TNBC.
  • To investigate the role of lipid metabolism in TNBC progression.
  • To combine genomic, functional, and lipidomic analyses.

Main Methods:

  • Utilized a large panel of human breast cancer cell lines and patient samples.
  • Performed comprehensive lipid profiling to analyze metabolic reprogramming.
  • Conducted mechanistic studies to link lipid profiles to cancer cell properties.

Main Results:

  • Phospholipid metabolism is reprogrammed in TNBC cells.
  • Patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is overexpressed in TNBC.
  • PNPLA8 silencing disrupted phospholipid metabolism and affected cell viability, migration, and antioxidation.

Conclusions:

  • PNPLA8 is a key regulator of phospholipid metabolic reprogramming in TNBC.
  • PNPLA8 influences malignant phenotypes including cell viability and migration.
  • PNPLA8 represents a potential novel molecular treatment target for TNBC.

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.5K
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...
3.6K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K
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...
6.3K
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...
3.8K
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...
4.5K