CXCR6/CXCL16 functions as a regulator in metastasis and progression of cancer.
Metastasis is considered the obvious mark for most aggressive cancers. However, little is known about the molecular mechanism of the regulation of cancer metastasis. Recent evidence increasingly suggests that the interaction between chemokines and chemokine receptors is pivotal in the process of metastasis. The chemokine receptor CXCR4 and its ligand CXCL12, for example, have been reported to play a vital role in cancer metastasis. Another chemokine and chemokine receptor pair, the CXCL16/CXCR6 axis, has been studied by several independent research groups. Here, we summarize recent advances in our knowledge of the function of CXC chemokine receptor CXCR6 and its ligand CXCL16 in regulating metastasis and invasion of cancer. CXCR6 and CXCL16 are up-regulated in multiple cancer tissue types and cancer cell lines relative to normal tissues and cell lines. In addition, both CXCR6 and CXCL16 levels increase as tumor malignancy increases. Trans-membranous CXCL16 chemokine reduces proliferation while soluble CXCL16 chemokine enhances proliferation and migration. TM-CXCL16 functions as an inducer for lymphocyte build-up around tumor sites. High trans-membranous CXCL16 expression correlates with a good prognosis. Moreover, the Akt/mTOR signal pathway is involved in activating the CXCR6/CXCL16 axis. These findings suggest multiple opportunities for blocking the CXCR6/CXCL16 axis and the Akt/mTOR signal pathway in novel cancer therapies.
Deng
Ling
L
Department of Radiation Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
Chen
Nianyong
N
Li
Yan
Y
Zheng
Hong
H
Lei
Qianqian
Q
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000502:physiology; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000209:etiology*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000502:physiology*; D051116:Receptors, Scavenger / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D054428:Chemokine CX3CL1; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D047908:Intracellular Signaling Peptides and Proteins; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases