Related Experiment Video

Updated: Feb 16, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

35.9K

SEC-induced activation of ANXA7 GTPase suppresses prostate cancer metastasis

ShuYan Liu1, Xiao Li1, ZhaoMin Lin2

  • 1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.

Cancer Letters
|December 17, 2017
PubMed

Insights

A novel small molecule SEC activates Annexin A7 GTPase (ANXA7), inhibiting prostate cancer metastasis. This occurs via the AMPK/mTORC1/STAT3 pathway, even when RKIP is low.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Annexin A7 (ANXA7) functions as a tumor suppressor in prostate cancer, with its activated GTPase promoting apoptosis.
  • The metastatic suppressor RKIP is downregulated in prostate cancer metastases, and its interaction with proteins can inhibit their activation.
  • The precise role and mechanism of ANXA7 GTPase in prostate cancer metastasis remain unclear.

Purpose of the Study:

  • To investigate the mechanism by which ANXA7 GTPase influences prostate cancer metastasis.
  • To determine the effect of RKIP on ANXA7 GTPase activation.
  • To evaluate the therapeutic potential of activating ANXA7 GTPase using a small molecule SEC.

Main Methods:

  • Activation of ANXA7 GTPase using the small molecule SEC.
  • Analysis of downstream signaling pathways including AMPK, mTORC1, and STAT3.
  • Assessment of pro-metastatic gene expression (CCL2, APLN, IL6ST).
  • Investigation of RKIP interaction with ANXA7.
  • In vivo orthotopic analysis of prostate cancer metastasis.

Main Results:

  • SEC-induced ANXA7 GTPase activation significantly inhibited prostate cancer metastasis.
  • Activated ANXA7 promoted AMPK phosphorylation, leading to reduced mTORC1 activity and suppressed STAT3 nuclear translocation.
  • RKIP was found to interact with ANXA7, impairing SEC-mediated activation and downstream signaling.
  • SEC treatment suppressed prostate cancer cell metastasis in vivo.
  • Downregulation of pro-metastatic genes (CCL2, APLN, IL6ST) was observed.

Conclusions:

  • SEC-induced ANXA7 GTPase activation is a viable strategy to suppress prostate cancer metastasis, particularly in cases with low RKIP expression.
  • The mechanism involves the AMPK/mTORC1/STAT3 signaling pathway.
  • This study provides novel insights into targeting ANXA7 for prostate cancer therapy.
Keywords:
AMPKANXA7 GTPaseMetastasisProstate cancerRKIP

More Related Videos

RhoC GTPase Activation Assay09:58

RhoC GTPase Activation Assay

Published on: August 22, 2010

13.1K
The Soft Agar Colony Formation Assay08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

113.9K

Related Concept Videos

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...
7.4K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
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...
5.3K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.7K
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...
8.7K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
18.7K