ANXA7-GTPase as Tumor Suppressor: Mechanisms and Therapeutic Opportunities.
Chromosomal abnormalities, including homozygous deletions and loss of heterozygosity at 10q, are commonly observed in most human tumors, including prostate, breast, and kidney cancers. The ANXA7-GTPase is a tumor suppressor, which is frequently inactivated by genomic alterations at 10q21. In the last few years, considerable amounts of data have accumulated describing inactivation of ANXA7-GTPase in a variety of human malignancies and demonstrating the tumor suppressor potential of ANXA7-GTPase. ANXA7-GTPase contains a calcium binding domain that classifies it as a member of the annexin family. The cancer-specific expression of ANXA7-GTPase, coupled with its importance in regulating cell death, cell motility, and invasion, makes it a useful diagnostic marker of cancer and a potential target for cancer treatment. Recently, emerging evidence suggests that ANXA7-GTPase is a critical factor associated with the metastatic state of several cancers and can be used as a risk biomarker for HER2 negative breast cancer patients. Cross talk between ANXA7, PTEN, and EGFR leads to constitutive activation of PI3K-AKT signaling, a central pathway of tumor cell survival and proliferation. This review focuses on the recent progress in understanding the tumor suppressor functions of ANXA7-GTPase emphasizing the role of this gene in Ca2+metabolism, and exploring opportunities for function as an example of a calcium binding GTPase acting as a tumor suppressor and opportunities for ANXA7-GTPase gene cancer therapy.
Department of Anatomy, Physiology and Genetics, Institute for Molecular Medicine, Center for Medical Proteomics, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Ximena
X
Leighton
Department of Anatomy, Physiology and Genetics, Institute for Molecular Medicine, Center for Medical Proteomics, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Ofer
O
Eidelman
Department of Anatomy, Physiology and Genetics, Institute for Molecular Medicine, Center for Medical Proteomics, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Catherine
C
Jozwik
Department of Anatomy, Physiology and Genetics, Institute for Molecular Medicine, Center for Medical Proteomics, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Harvey B
HB
Pollard
Department of Anatomy, Physiology and Genetics, Institute for Molecular Medicine, Center for Medical Proteomics, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. meera.srivastava@usuhs.edu.
Meera
M
Srivastava
D017310:Annexin A7 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002118:Calcium / Q000378:metabolism; D002879:Chromosomes, Human, Pair 10; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019656:Loss of Heterozygosity; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D017310:Annexin A7; D002118:Calcium; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human
ANXA7-GTPase; Apoptosis; Calcium; Cancer; Tumor suppressor gene