Related Experiment Video

Updated: Oct 27, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.4K

SREBP1 site 1 protease inhibitor PF-429242 suppresses renal cell carcinoma cell growth

Tong-Bing Wang1, Mei Geng2, Hua Jin3

  • 1Department of Urology, People's Hospital of Yangzhong City, Yangzhong, China.

Cell Death & Disease
|July 21, 2021
PubMed

Insights

Targeting site 1 protease (S1P) with PF-429242 effectively inhibits renal cell carcinoma (RCC) growth, migration, and invasion by inducing apoptosis in cancer cells and xenografts.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Renal cell carcinoma (RCC) exhibits heightened lipogenesis and cholesterol synthesis.
  • Sterol regulatory element-binding protein-1 (SREBP1) activation involves cleavage by site 1 protease (S1P).

Purpose of the Study:

  • To evaluate the efficacy of PF-429242, a potent S1P inhibitor, in preclinical models of renal cell carcinoma.
  • To investigate the role of S1P in RCC cell proliferation, migration, invasion, and apoptosis.

Main Methods:

  • Treatment of established and primary human RCC cells with PF-429242.
  • S1P inhibition using shRNA or CRISPR/Cas9 gene editing.
  • Overexpression studies of SREBP1 and S1P.
  • In vivo efficacy studies using RCC xenografts in mice.
  • Analysis of SREBP1, S1P, and LDLR expression in human RCC tissues.

Main Results:

  • PF-429242 significantly inhibited RCC cell proliferation, migration, and invasion, while inducing apoptosis.
  • S1P inhibition via shRNA or CRISPR/Cas9 also suppressed RCC cell growth and promoted apoptosis.
  • Overexpression of SREBP1 or S1P enhanced RCC cell proliferation and migration.
  • PF-429242 and S1P shRNA effectively inhibited RCC xenograft growth in vivo.
  • SREBP1, S1P, and LDLR were upregulated in human RCC tissues.

Conclusions:

  • Targeting S1P with PF-429242 demonstrates significant anti-cancer activity against renal cell carcinoma in vitro and in vivo.
  • S1P is a promising therapeutic target for renal cell carcinoma treatment.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.2K
Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

11.6K

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.3K
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...
5.1K
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...
4.2K
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...
4.0K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
36.7K