title: Tissue invasion and metastasis: Molecular, biological and clinical perspectives.
abstract: Cancer is a key health issue across the world, causing substantial patient morbidity and mortality. Patient prognosis is tightly linked with metastatic dissemination of the disease to distant sites, with metastatic diseases accounting for a vast percentage of cancer patient mortality. While advances in this area have been made, the process of cancer metastasis and the factors governing cancer spread and establishment at secondary locations is still poorly understood. The current article summarizes recent progress in this area of research, both in the understanding of the underlying biological processes and in the therapeutic strategies for the management of metastasis. This review lists the disruption of E-cadherin and tight junctions, key signaling pathways, including urokinase type plasminogen activator (uPA), phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT), focal adhesion kinase (FAK), β-catenin/zinc finger E-box binding homeobox 1 (ZEB-1) and transforming growth factor beta (TGF-β), together with inactivation of activator protein-1 (AP-1) and suppression of matrix metalloproteinase-9 (MMP-9) activity as key targets and the use of phytochemicals, or natural products, such as those from Agaricus blazei, Albatrellus confluens, Cordyceps militaris, Ganoderma lucidum, Poria cocos and Silybum marianum, together with diet derived fatty acids gamma linolenic acid (GLA) and eicosapentanoic acid (EPA) and inhibitory compounds as useful approaches to target tissue invasion and metastasis as well as other hallmark areas of cancer. Together, these strategies could represent new, inexpensive, low toxicity strategies to aid in the management of cancer metastasis as well as having holistic effects against other cancer hallmarks.
authors: Cardiff University, Cardiff, United Kingdom. Electronic address: jiangw@cf.ac.uk.
authors: W G
authors: WG
authors: Jiang
authors: Cardiff University, Cardiff, United Kingdom.
authors: A J
authors: AJ
authors: Sanders
authors: National Cancer Center, Tokyo, Japan.
authors: M
authors: M
authors: Katoh
authors: University Hospital Schleswig-Holstein, Lübeck, Germany.
authors: H
authors: H
authors: Ungefroren
authors: University Hospital Schleswig-Holstein, Lübeck, Germany.
authors: F
authors: F
authors: Gieseler
authors: University of Michigan, Ann Arbor, MI, USA.
authors: M
authors: M
authors: Prince
authors: Royal Adelaide Hospital, Adelaide, Australia.
authors: S K
authors: SK
authors: Thompson
authors: Department of Molecular Medicine and Medical Biotechnology (DMMBM), University of Naples Federico II, Naples, Italy; CEINGE Biotecnologie Avanzate, Naples, Italy.
authors: M
authors: M
authors: Zollo
authors: CEINGE Biotecnologie Avanzate, Naples, Italy.
authors: D
authors: D
authors: Spano
authors: University of Nebraska Medical Center, Omaha, USA.
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authors: Dhawan
authors: Purdue Research Park, Indianapolis, IN, USA.
authors: D
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authors: Sliva
authors: University of Miami, Miami, FL, USA.
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authors: Subbarayan
authors: University of Miami, Miami, FL, USA.
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authors: Sarkar
authors: Nara Medical University, Kashihara, Japan.
authors: K
authors: K
authors: Honoki
authors: Nara Medical University, Kashihara, Japan.
authors: H
authors: H
authors: Fujii
authors: Physics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Athens, Greece.
authors: A G
authors: AG
authors: Georgakilas
authors: University of Florence, Florence, Italy.
authors: A
authors: A
authors: Amedei
authors: University of Florence, Florence, Italy.
authors: E
authors: E
authors: Niccolai
authors: United Arab Emirates University, Al Ain, United Arab Emirates and Faculty of Science, Cairo University, Egypt.
authors: A
authors: A
authors: Amin
authors: United Arab Emirates University, Al Ain, United Arab Emirates and Faculty of Science, Cairo University, Egypt.
authors: S S
authors: SS
authors: Ashraf
authors: Cardiff University, Cardiff, United Kingdom.
authors: L
authors: L
authors: Ye
authors: University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors: W G
authors: WG
authors: Helferich
authors: University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors: X
authors: X
authors: Yang
authors: Creighton University, Omaha, NE, USA.
authors: C S
authors: CS
authors: Boosani
authors: SASTRA University, Thanjavur, India.
authors: G
authors: G
authors: Guha
authors: University of Rome Tor Vergata, Rome, Italy.
authors: M R
authors: MR
authors: Ciriolo
authors: University of Rome Tor Vergata, Rome, Italy.
authors: K
authors: K
authors: Aquilano
authors: Ovarian and Prostate Cancer Research Trust Laboratory, Surrey, United Kingdom.
authors: S
authors: S
authors: Chen
authors: Wayne State University, Detroit, MI, USA.
authors: A S
authors: AS
authors: Azmi
authors: University of Glasgow, Glasgow, United Kingdom.
authors: W N
authors: WN
authors: Keith
authors: University of Glasgow, Glasgow, United Kingdom.
authors: A
authors: A
authors: Bilsland
authors: SASTRA University, Thanjavur, India.
authors: D
authors: D
authors: Bhakta
authors: New York Medical College, Valhalla, NY, USA.
authors: D
authors: D
authors: Halicka
authors: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors: S
authors: S
authors: Nowsheen
authors: University Campus Bio-Medico, Rome, Italy.
authors: F
authors: F
authors: Pantano
authors: University Campus Bio-Medico, Rome, Italy.
authors: D
authors: D
authors: Santini
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D015820:Cadherins / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins
keywords: Cancer metastasis; Cancer therapy; Invasion