AGO2 involves the malignant phenotypes and FAK/PI3K/AKT signaling pathway in hypopharyngeal-derived FaDu cells

Yanhui Zhang1, Baoxin Wang2, Xinwei Chen2

  • 1Department of Otolaryngology Head and Neck Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Oncotarget
|September 15, 2017
PubMed

Insights

Argonaute 2 (AGO2) is overexpressed in hypopharyngeal cancer, promoting tumor growth and progression. Reducing AGO2 hinders cancer cell proliferation and migration, suggesting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Argonaute 2 (AGO2) protein overexpression is observed in head and neck squamous cell carcinoma.
  • The specific role of AGO2 in hypopharyngeal cancer progression remains unclear.

Purpose of the Study:

  • To investigate the expression and function of AGO2 in hypopharyngeal cancer.
  • To elucidate the molecular mechanisms underlying AGO2's role in hypopharyngeal cancer tumorigenesis.

Main Methods:

  • Quantitative analysis of AGO2 expression in hypopharyngeal cancer tissues versus adjacent noncancerous tissues.
  • Functional studies involving stable knockdown of AGO2 in hypopharyngeal cancer cell lines (FaDu).
  • Assessment of cell proliferation, migration, invasion, cell cycle, and apoptosis following AGO2 knockdown.
  • Analysis of the FAK/PI3K/AKT signaling pathway.

Main Results:

  • AGO2 expression is significantly higher in hypopharyngeal cancer tissues compared to normal tissues.
  • Elevated AGO2 levels correlate with aggressive clinicopathologic features and poor patient outcomes.
  • Stable knockdown of AGO2 suppressed cell proliferation, migration, and invasion.
  • AGO2 knockdown induced cell cycle arrest and apoptosis.
  • Inhibition of the FAK/PI3K/AKT signaling pathway was observed after AGO2 knockdown.

Conclusions:

  • AGO2 acts as an oncogene in hypopharyngeal cancer, driving tumorigenesis and progression.
  • AGO2 holds potential value for molecular diagnosis, targeted therapy, and prognosis evaluation in hypopharyngeal cancer.

Related Concept Videos

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...
5.8K
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...
4.9K
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...
5.3K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K
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...
7.4K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.7K