Autocrine Motility Factors in Tumorigenesis and Metastasis
Summary
Autocrine motility factor (AMF) is a multifunctional protein originally characterised as phosphoglucose isomerase (PGI) in glycolysis. Beyond its metabolic role, AMF is secreted by cancer cells and binds to its receptor (AMFR/gp78) on the same cell to promote motility, invasion and metastatic spread. Binding of AMF to AMFR activates signal cascades such as extracellular signal-regulated kinases (ERK) and leads to cytoskeletal reorganisation, enhanced expression of matrix remodelling enzymes and modulation of cell cycle regulators. Tumour microenvironmental cues, notably hypoxia, further up-regulate AMF expression via hypoxia-inducible factor-1α (HIF-1α), reinforcing metastatic potential. Clinically, elevated AMF and AMFR levels correlate with aggressive disease and poor prognosis across diverse malignancies, rendering this axis a promising biomarker and therapeutic target. Ongoing research seeks to intercept AMF signalling directly, explore its interplay with cytokines and immune cells, and integrate AMF status into precision-medicine strategies aimed at limiting dissemination and improving patient outcomes.
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Autocrine Motility Factors in Tumorigenesis and Metastasis publication trend
The graph below shows the total number of articles in autocrine motility factors in tumorigenesis and metastasis across all publications each year (not limited to Nature Index journals).
Technical terms
Autocrine motility factor (AMF): A secreted form of phosphoglucose isomerase that stimulates cell movement by binding to its own receptor.
Phosphoglucose isomerase (PGI): A glycolytic enzyme converting glucose-6-phosphate to fructose-6-phosphate and, when secreted, functioning as AMF.
Autocrine motility factor receptor (AMFR/gp78): A cell surface glycoprotein that binds AMF and initiates downstream signalling.
Hypoxia-inducible factor-1α (HIF-1α): A transcription factor stabilised under low oxygen that drives expression of genes such as AMF.
Extracellular signal-regulated kinases (ERK): A protein kinase cascade activated by AMF–AMFR interaction, promoting gene expression and motility.
Interleukin-8 (IL-8): A pro-inflammatory cytokine induced by AMF signalling that further enhances tumour cell migration.
References
- GPI Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma. Frontiers in Oncology (2021).
- Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor. Journal of Biological Chemistry (1991).
- Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells. British Journal of Cancer (2002).
- Regulation of Cell Proliferation by Autocrine Motility Factor/Phosphoglucose Isomerase Signaling*. Journal of Biological Chemistry (2003).
- GPI: An indicator for immune infiltrates and prognosis of human breast cancer from a comprehensive analysis. Frontiers in Endocrinology (2022).
- Phosphoglucose Isomerase/Autocrine Motility Factor Promotes Melanoma Cell Migration through ERK Activation Dependent on Autocrine Production of Interleukin-8*. Journal of Biological Chemistry (2009).
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