Related Experiment Video

Updated: May 10, 2025

RhoC GTPase Activation Assay
09:58

RhoC GTPase Activation Assay

Published on: August 22, 2010

12.4K

SMC4 Promotes Prostate Cancer Cell Proliferation and Metastasis via the Rheb/mTOR Pathway

Wei Zhang1,2, Siyuan Qin3, Xiaokang Li4

  • 1School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, 518053, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 25, 2025
PubMed

Insights

Structural maintenance of chromosome protein 4 (SMC4) promotes prostate cancer metastasis by enhancing glycolysis and interacting with GLUT1. Inhibiting SMC4 reduces cancer cell proliferation, migration, and metastasis via the Rheb/mTOR pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer metastasis remains a significant clinical challenge.
  • The precise role of Structural Maintenance of Chromosome protein 4 (SMC4) in prostate cancer progression is not fully understood.
  • Aberrant SMC4 expression is linked to metastatic progression in prostate cancer.

Purpose of the Study:

  • To elucidate the functional role of SMC4 in prostate cancer metastasis.
  • To investigate the molecular mechanisms by which SMC4 influences cancer cell behavior.
  • To identify potential therapeutic targets for prostate cancer treatment.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) database for SMC4 expression patterns.
  • CRISPR/Cas9-mediated SMC4 gene knockdown in RM1-LM cells.
  • In vitro assays for cell proliferation and migration.
  • In vivo murine metastasis model.
  • RNA sequencing (RNA-seq) and KEGG pathway enrichment analysis.
  • Immunoprecipitation-Mass Spectrometry (IP-MS) to identify SMC4 interactors.
  • Co-immunoprecipitation (Co-IP) and glycolytic rate assays.

Main Results:

  • SMC4 knockdown significantly reduced prostate cancer cell proliferation and migration in vitro.
  • SMC4 knockdown diminished lung metastasis capabilities in a murine model.
  • SMC4 knockdown inhibited the Rheb/mTOR signaling pathway and reduced ATP production.
  • SMC4 was found to interact with Glucose Transporter 1 (GLUT1), impacting cellular glycolysis.
  • KEGG analysis revealed enrichment of cancer and metabolic pathways.

Conclusions:

  • SMC4 promotes prostate cancer cell metastasis through interaction with GLUT1 and modulation of the Rheb/mTOR pathway.
  • Targeting SMC4 or its interaction with GLUT1 may represent a novel therapeutic strategy for metastatic prostate cancer.
  • SMC4 plays a critical role in regulating cancer cell metabolism and metastatic potential.
Keywords:
GLUT1SMC4metastasisprostate cancer

More Related Videos

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

1.4K
Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model06:32

Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model

Published on: November 4, 2022

4.3K

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...
3.6K
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
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...
4.3K
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...
4.9K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.1K
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...
6.3K