NSD2 Promotes Renal Cancer Progression Through Stimulating Akt/Erk Signaling

Xu Han1, Lianhua Piao2, Xiaoshuang Xu2

  • 1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People's Republic of China.

Abstract

Insights

Nuclear receptor SET domain-containing 2 (NSD2) is overexpressed in clear cell renal cell carcinoma (ccRCC), promoting cancer progression by activating Akt/Erk signaling. NSD2 inhibition suppressed tumor growth and improved survival in ccRCC models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Nuclear receptor SET domain-containing 2 (NSD2) is a histone lysine methyltransferase.
  • The role of NSD2 in clear cell renal cell carcinoma (ccRCC) requires further investigation.

Purpose of the Study:

  • To investigate the biological role and clinical significance of NSD2 in ccRCC.
  • To elucidate the underlying molecular mechanisms by which NSD2 influences ccRCC progression.

Main Methods:

  • Bioinformatic analysis of NSD2 expression in ccRCC using GEO and OncoLnc databases.
  • Immunohistochemistry (IHC) to assess NSD2 protein levels in ccRCC tissues.
  • In vitro (cell lines) and in vivo (xenograft) assays to evaluate the functional impact of NSD2 modulation on ccRCC progression, including proliferation, apoptosis, and signaling pathways (Akt/Erk).

Main Results:

  • NSD2 is significantly overexpressed in ccRCC tissues and cell lines, distinguishing ccRCC from normal samples.
  • High NSD2 expression correlates with shorter overall survival (OS) in ccRCC patients.
  • NSD2 knockdown inhibits ccRCC cell proliferation, induces apoptosis by downregulating Bcl-2 and upregulating Bax, and suppresses tumor growth in vivo, mediated by Akt/Erk signaling inhibition.

Conclusions:

  • NSD2 acts as an oncogenic factor in ccRCC progression.
  • Activation of Akt/Erk signaling by NSD2 is a key mechanism driving ccRCC.
  • Targeting NSD2 may represent a potential therapeutic strategy for ccRCC.

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...
5.1K
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
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.6K
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...
7.7K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.2K