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Autocrine motility factor and its receptor expression in musculoskeletal tumors

Kosei Nakajima1,2, Avraham Raz3

  • 1Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo 104-0045, Japan.

Journal of Bone Oncology
|October 26, 2020
PubMed

Insights

Autocrine motility factor (AMF) and its receptor (AMFR) signaling drives aggressive musculoskeletal tumors. Inhibiting AMF and AMFR presents a potential therapeutic strategy for these challenging cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Aggressive malignant musculoskeletal tumors pose significant clinical challenges.
  • Autocrine motility factor (AMF) and its receptor (AMFR) signaling are implicated in tumor progression by altering the bone microenvironment.
  • AMF/GPI and AMFR/gp78 are moonlighting proteins involved in cellular metabolism and protein degradation, contributing to increased metabolic turnover.

Purpose of the Study:

  • To review the role of AMF-AMFR signaling in malignant musculoskeletal tumors.
  • To highlight the potential of targeting AMF and AMFR as a therapeutic strategy.
  • To underscore the unmet medical need for novel treatments in this area.

Main Methods:

  • Literature review of studies on AMF and AMFR in musculoskeletal tumors.
  • Analysis of a large-scale cohort study examining AMF and AMFR expression in various tumor types.
  • Examination of cellular data linking tumor cells and bone microenvironment components via AMF-AMFR signaling.

Main Results:

  • Musculoskeletal tumors, including osteosarcoma and multiple myeloma, show elevated AMF expression.
  • Multiple myeloma patients exhibit high AMFR expression.
  • Cellular data confirms AMF expression in tumors and AMFR expression in the bone microenvironment, indicating cross-talk.

Conclusions:

  • AMF-AMFR signaling represents a critical link between musculoskeletal tumors and the skeletal environment.
  • Pharmacological inhibition of AMF and AMFR is a promising therapeutic avenue.
  • Targeting this pathway addresses a significant unmet medical need in managing aggressive malignant musculoskeletal tumors.
Keywords:
AMF (Autocrine Motility Factor: Glucose-6-Phosphate Isomerase)AMFR (Autocrine Motility Factor Receptor: gp78)Bone microenvironmentMusculoskeletal tumors

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