[NUSAP1 promotes lung cancer progression by activating AKT/mTOR signaling pathway]

Z Yu1, X M Li2, M Huai3

  • 1Department of Cardiothoracic Medicine, North China Petroleum Administration Bureau General Hospital, Renqiu 062552, China.

Insights

Nucleolar and spindle associated protein 1 (NUSAP1) knockdown inhibits lung cancer cell growth and spread. This occurs by reducing the AKT/mTOR pathway, leading to increased cancer cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Lung cancer remains a leading cause of cancer-related mortality worldwide.
  • Understanding the molecular mechanisms driving lung cancer progression is crucial for developing effective therapies.
  • Nucleolar and spindle associated protein 1 (NUSAP1) has been implicated in cell division and cancer, but its specific role in lung cancer requires further elucidation.

Purpose of the Study:

  • To investigate the inhibitory effects of targeting nucleolar and spindle associated protein 1 (NUSAP1) in lung cancer.
  • To elucidate the underlying molecular mechanisms, particularly the involvement of the AKT/mTOR signaling pathway.

Main Methods:

  • Utilized A549 lung cancer cells transfected with NUSAP1 siRNA.
  • Assessed cell proliferation, migration, invasion, and apoptosis using CCK8, Transwell assays, and flow cytometry.
  • Analyzed protein expression related to apoptosis and the AKT/mTOR pathway via Western blot.

Main Results:

  • NUSAP1 knockdown significantly inhibited proliferation, migration, and invasion of A549 cells.
  • NUSAP1 knockdown significantly increased apoptosis in A549 cells.
  • Downregulation of NUSAP1 led to increased Bax and active-caspase 3, and decreased Bcl-2, P70, and phosphorylation of AKT/mTOR.

Conclusions:

  • NUSAP1 knockdown demonstrates significant anti-cancer effects in lung cancer cells.
  • The observed effects are mediated through the suppression of the AKT/mTOR signaling pathway.
  • Targeting NUSAP1 represents a potential therapeutic strategy for lung cancer treatment.

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...
4.5K
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...
5.0K
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...
5.0K
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...
7.5K
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...
11.2K
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...
7.0K