Metformin inhibits mTOR and c-Myc by decreasing YAP protein expression in OSCC cells

Ying Wang1, Yafei Zhang1, Xiaomei Feng1

  • 1Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.

Oncology Reports
|March 2, 2021
PubMed

Insights

Metformin, an antidiabetic drug, suppresses oral squamous cell carcinoma (OSCC) by inhibiting Yes-associated protein (YAP). This action impacts cell cycle, apoptosis, and key proteins like mTOR and c-Myc, offering a new therapeutic avenue for OSCC.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Metformin exhibits anticancer properties against various cancers, including oral squamous cell carcinoma (OSCC).
  • The role of Yes-associated protein (YAP), crucial in OSCC development, in metformin's anticancer effects remains underexplored.

Purpose of the Study:

  • To investigate the molecular interplay between metformin and YAP in OSCC cells.
  • To elucidate how metformin influences YAP-mediated pathways in OSCC.

Main Methods:

  • OSCC cell lines (CAL27, SCC25) were treated with metformin.
  • Cell proliferation and apoptosis were assessed using CCK-8 and flow cytometry.
  • Protein levels of YAP, mTOR, p-mTOR, and c-Myc were analyzed via western blotting.

Main Results:

  • Metformin altered the cell cycle and apoptosis in OSCC cells.
  • Modulating YAP expression affected metformin's impact on cell cycle and apoptosis.
  • Metformin reduced YAP, mTOR, p-mTOR, and c-Myc protein levels; YAP overexpression counteracted this effect.

Conclusions:

  • Metformin suppresses OSCC by inhibiting YAP protein expression.
  • Metformin targets YAP-mediated signaling, affecting mTOR and c-Myc pathways.
  • These findings highlight YAP as a potential mediator of metformin's anticancer activity in OSCC.

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...
4.1K
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...
4.6K
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...
4.9K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.3K
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
437
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K