Related Experiment Video

Updated: Sep 7, 2025

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

253

Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation

Fangzhou Li1, Xufeng Peng1, Jiale Zhou1

  • 1Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No.1630 Dong Fang Road, Shanghai, 200127, China.

Journal of Cancer Research and Clinical Oncology
|June 17, 2022
PubMed
Abstract

Insights

Mitogen-activated protein kinase kinase 5 (MEK5) is upregulated in clear cell renal cell carcinoma (ccRCC), promoting tumor growth. Inhibiting MEK5 with BIX02189 shows promise as a targeted therapy for ccRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Clear cell renal cell carcinoma (ccRCC) is a significant health concern.
  • Understanding the molecular mechanisms driving ccRCC progression is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role and expression of MEK5 signaling in ccRCC.
  • To determine the interplay between MEK5 and mTOR signaling pathways in ccRCC.

Main Methods:

  • Comparative analysis of MEK5 expression in ccRCC versus normal tissues using public databases (ONCOMINE, TCGA) and clinical samples.
  • In vitro assays (CCK8, wound-healing, clone formation) to assess the impact of MEK5 modulation and BIX02189 on ccRCC cell behavior.
  • Western blotting to elucidate MEK5's effect on the mTOR pathway.
  • In vivo evaluation of BIX02189 efficacy and safety in a murine subcutaneous tumor model.

Main Results:

  • MEK5 expression is significantly elevated in ccRCC tissues compared to normal tissues.
  • MEK5 knockdown inhibits ccRCC cell proliferation, migration, and clone formation, while overexpression enhances these processes.
  • MEK5 activation leads to increased mTOR signaling. The MEK5 inhibitor BIX02189 effectively suppresses tumor growth, induces cell cycle arrest and apoptosis, and inhibits migration in vitro and in vivo, with a favorable safety profile.

Conclusions:

  • Aberrant MEK5 upregulation in ccRCC activates the mTOR pathway, driving tumor cell proliferation, cell cycle progression, migration, and clone formation.
  • Targeted inhibition of MEK5 using agents like BIX02189 presents a potential therapeutic strategy for ccRCC patients.
Keywords:
Clear cell renal cell carcinomaInhibitorMEK5mTOR

More Related Videos

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane05:36

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

9.1K
Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy11:27

Modeling Spontaneous Metastatic Renal Cell Carcinoma mRCC in Mice Following Nephrectomy

Published on: April 29, 2014

16.8K

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...
3.9K
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...
3.9K
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...
4.6K
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...
6.0K
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...
4.9K
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...
6.6K