NCKAP1 Inhibits the Progression of Renal Carcinoma via Modulating Immune Responses and the PI3K/AKT/mTOR Signaling

Xin Zhang1, Jianqing Ye2, Lixiang Sun1

  • 1Central Laboratory, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, China.

Insights

Nck-associated protein 1 (NCKAP1) is crucial in kidney cancer. Lower NCKAP1 levels correlate with poor prognosis and impact immune cell infiltration, suggesting it as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Nck-associated protein 1 (NCKAP1) is vital for cellular functions and cancer progression.
  • Its role in renal cancer development and immune regulation remains unclear.

Purpose of the Study:

  • To investigate NCKAP1's function in renal cancer progression and immune modulation.
  • To explore NCKAP1 as a potential biomarker and therapeutic target in kidney cancer.

Main Methods:

  • Pancancer analysis of NCKAP1 expression and variations using UALCAN and cBioPortal.
  • Assessment of immune cell infiltration via ssGSEA and single-cell RNA sequencing.
  • RNA sequencing of NCKAP1-overexpressing cells and pathway analysis (PI3K/AKT/mTOR).

Main Results:

  • NCKAP1 expression varies across cancers; reduced levels in renal cancer correlate with poorer patient outcomes.
  • NCKAP1 expression patterns identified in distinct renal cancer cell lineages.
  • Significant correlation found between NCKAP1 and immune cell infiltration in the kidney tumor microenvironment.
  • NCKAP1 suppresses renal cancer cell growth and tumor development via the PI3K/AKT/mTOR pathway.

Conclusions:

  • NCKAP1 plays a significant role in renal cancer progression and immune response.
  • NCKAP1 acts as a tumor suppressor in kidney cancer.
  • NCKAP1 is a promising predictive marker and therapeutic target for renal 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...
3.3K
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...
3.7K
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...
4.6K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
145
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...
6.2K
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...
8.6K