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CXCL12 (chemokine (C-X-C motif) ligand 12)

Written2015-08Giulia Gentile, Maria Guarnaccia, Sebastiano Cavallaro
Functional Genomics Unit, Institute of Neurogical Sciences, National Research Council, Catania, Italy

Abstract Review on CXCL12, with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords CXCL12; Lung cancer; Breast cancer; Human Immunodeficiency Virus-type 1 (HIV-1) infection; WHIM Syndrome; Autoimmune Diseases

(Note : for Links provided by Atlas : click)


Alias (NCBI)SDF-1
HGNC (Hugo) CXCL12
HGNC Alias symbSCYB12
HGNC Previous nameSDF1A
HGNC Previous namestromal cell-derived factor 1
 chemokine (C-X-C motif) ligand 12
LocusID (NCBI) 6387
Atlas_Id 40219
Location 10q11.21  [Link to chromosome band 10q11]
Location_base_pair Starts at 44377067 and ends at 44385097 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping CXCL12.png]
Local_order Molecular Location: Chromosome 10; base pairs 44,865,601-44,880,545 reverse strand, in the February 2009 hg19 human assembly (GRCh37). According to UCSC Genome Browser on Human Feb. 2009 assembly (GRCh37/hg19), genes flanking CXCL12 on 10q11.21, in centromere to telomere direction, are ZNF32 (zinc finger protein 32), HNRNPA3P1 (heterogeneous nuclear ribonucleoprotein A3 pseudogene 1), CXCL12, THEM72 (transmembrane protein 72), RASSF4 (Ras association (RalGDS/AF-6) domain family member 4).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ANGPT1 (8q23.1)::CXCL12 (10q11.21)CXCL12 (10q11.21)::CXCL12 (10q11.21)CXCL12 (10q11.21)::NKAIN3 (8q12.3)
ECD (10q22.1)::CXCL12 (10q11.21)ECD (10q22.2)::CXCL12 (10q11.21)IPMK (10q21.1)::CXCL12 (10q11.21)
Note Synonyms: Stromal cell-derived factor 1, Pre-B cell growth-stimulating factor, Intercrine reduced in hepatomas.


  Figure 1 Schematic structure of the four exons of human CXCL12 (exon1: 153bp; exon2: 118bp; exon3: 87bp; exon4: 3191bp). Two of them are made up not only of coding regions (in green color) but also of non-coding ones (in red color).
Description The CXCL12 gene consists of 4 exons spanning 14.94 kb on the chromosome 10 at band q11.21 (reverse strand) (Figure 1).
Transcription Alternative splicing results in eight transcript variants (Table 1), as shown in Ensembl database. Among them, six correspond to as many protein isoforms (Yu et al., 2006).
Pseudogene No known pseudogenes.


Description CXCL12 gene encodes a stromal cell-derived alpha chemokine, also known as SDF1, a member of the intercrine family. This family is defined by the location of the first two cysteine residues in the sequence, which are separated by one amino acid (C-X-C chemokine)(Hromas, 1997). Six protein isoforms have been identified in human: Alpha, Beta, Gamma, Delta, Epsilon and Theta (Table 2; Figure 2), produced by alternative splicing events (Yu et al., 2006). In particular Alpha and Beta isoforms, secreted as full-length molecules, undergo to post-translational modifications by a proteolytic cleavage, becoming respectively processed forms SDF-1-alpha(3-67) and SDF-1-beta(3-72)(De la Luz Sierra et al., 2004). The Beta isoform has been chosen as the canonical sequence and, together with Alpha isoform, is ubiquitously expressed in liver, pancreas and spleen. The Gamma Isoform is mainly expressed in heart, while the isoforms Delta, Epsilon and Theta are mainly expressed in pancreas. In the developmental stage, the isoform Alpha is ubiquitously expressed in fetal tissues, Beta and Delta isoforms in fetal spleen and liver, while Gamma and Theta isoforms are weakly detected in fetal kidney (Yu et al., 2006).
  Figure 2 The figure shows (A)the molecule processing of CXCL12 beta isoform sequence, in which the potential signal peptide is marked in red color while the polypeptide chain in blue color (data obtained from UniProtKB database);(B) the multiple sequence alignment of the six CXCL12 isoforms. For each isoform, after the 88 identical positions there are a certain number of different residues, highlighted in light blue color. (Alignment produced by CLC Sequence Viewer 7.0 from CLCbio - QIAGEN Company, using Clustal Omega multiple alignment program). SDF-1-alpha(3-67) and SDF-1-beta(3-72), processed by post-translational proteolytic cleavage, are marked by yellow and orange boxes respectively (data on both sequences belong to UniProtKB database).
Expression CXCL12 is widely expressed in a variety of tissue types, such as heart, liver, spleen, kidney, brain, skeletal muscle, endothelium, epithelium, lymphoid organs, stem cells as well as overexpressed in cancer cells (Kryczek et al., 2007; Teicher and Fricker, 2010).
Localisation Extracellular region.
Function The CXCL12 protein functions as a ligand for two seven-transmembrane receptors (7-TMRs). The first one is the chemokine (C-X-C motif) receptor 4 (CXCR4), a monogamous receptor that signals through heterotrimeric G proteins and beta-arrestin; the second one is the chemokine (C-X-C motif) receptor 7 (CXCR7), a non-monogamous receptor that does not activate G-protein-mediated signal transduction but signals only through beta-arrestin (Oberlin et al., 1996; Rajagopal et al., 2010; Sun et al., 2010; Zhu et al., 2012; Sanchez-Martin et al., 2013). In particular, CXCL12 has a higher affinity of binding to CXCR7 than to CXCR4 (Zhu et al., 2012), even if its affinity to CXCR7 seems to be reduced by the expression of CXCR4 at the membrane (Sanchez-Martin et al., 2013). CXCL12 is secreted in the extracellular space as monomeric and dimeric forms, which can trigger different effects on cell signaling (Ray et al., 2012). In fact, whereas CXCR4 binds both monomeric and dimeric forms, CXCR7 binds preferentially the dimeric one (Sanchez-Martin et al., 2013). For example, dimeric CXCL12 form induces calcium mobilization but fails to promote chemotaxis, which is induced by the monomer-based interactions (Ray et al., 2012; Sanchez-Martin et al., 2013). Many others cellular functions depend on CXCL12 activity, including embryogenesis, apoptosis and survival, immune response, tissue homeostasis, angiogenesis, calcium ion homeostasis, clathrin-mediated endocytosis, cytoskeletal rearrangement, cell proliferation and migration, tumor growth and metastasis (Vlahakis et al., 2002; Goda et al., 2006; Petit et al., 2007; Khan et al., 2008; Agle et al., 2010; Drury et al.,2010; Karin, 2010; Kremer, 2010; Sun et al., 2010; Zhu et al., 2012).
Homology The CXCL12 Gene Tree shows a great evolutionary conservation across species (Figure 3). The internal nodes of the phylogenetic tree are annotated for duplication (red boxes) and speciation (blue boxes) events, which correspond to paralogs and orthologs homologous genes respectively.
  Figure 3 The CXCL12 Gene Tree shows the maximum likelihood phylogenetic tree representing the evolutionary history of the CXCL12 gene, constructed using the alignment of a CXCL12 representative protein for each species (green bars). The Gene tree has been generated by Ensembl (GeneTree ENSGT00390000014056 - August 2015) using the Gene Orthology/Paralogy prediction method pipeline (Vilella et al., 2009).


Note NOTE It has been suggested that a single nucleotide polymorphism (SNP)in the 3' untranslated region of SDF-1-beta transcript is associated not only with a delayed onset (Winkler et al., 1998) and a modest protective effect against infection and progression of AIDS (Modi et al., 2005), but also with the early onset of type 1 diabetes (Dubois-Laforgue et al., 2001) and with an increased likelihood of developing several cancers (as lung, breast, colorectal and prostate)(Ma et al., 2012; Shi et al., 2013). This could be explained by an increased level and stability of SDF-1-beta transcript as effect of this mutation (Garcia-Moruja et al., 2009).
Somatic A SNP consisting of a G-to-A transition at position 801, counting from the ATG start codon in the 3' UTR of the Genbank reference sequence L36033, was represented in the SDF-1-beta transcript but not in the SDF-1-alpha transcript (Winkler et al., 1998). The mutation CXCL12-G801A-3 Prime UTR, also known as SDF1-3-prime-A, located at chromosome 10 position 44873550 on Assembly GRCh37, has been classified as pathogenic variant (dbSNP: rs387906400)related to the phenotype Human immunodeficiency virus type 1, resistance to (OMIM: 600835.0001).

Implicated in

Entity Lung cancer
Note The CXCL12 expression showed an increase in lung cancer cell lines (small cell lung cancers and non-small cell lung cancers) compared to non-malignant human bronchial epithelial cell ones. This overexpression was positively but weakly correlated with those of CXCR4 or CXCR7, suggesting that CXCL12 may differentially interact with its receptors depending on the cellular context (Imai et al., 2010). Furthermore, different evidences support the involvement of the CXCL12/CXCR4 axis, but not CXCL12/CXCR7, in the metastatic behavior of non-small cell lung cancer, suggesting their potential use as prognostic markers and drug targets (Paratore et al., 2011; Cavallaro, 2013; Choi et al., 2014).
Entity Breast cancer
Note The CXCL12 expression has been shown to stimulate breast cancer cells proliferation and promote tumor growth (Allinen et al., 2004; Duda et al., 2011). Moreover, a CXCL12 gene variant CXCL12-A (CXCL12-G801A, a single nucleotide polymorphism in the 3' untranslated region) was associated with an increased susceptibility to breast cancer (Dimberg et al., 2007). The interactions of CXCL12/CXCR4 seems to have a critical role in determining the metastatic destination of breast cancer metastasis (Muller et al., 2001; Hinton et al., 2011), while the CXCR7 expression has been linked to the ability of tumor cells to produce lung and brain metastasis (Sun et al., 2010). In a recent study, the expression profiles of the six CXCL12 isoforms and both receptors have been investigated in a large clinical cohort and common breast cancer cell lines. As result, isoform-specific differences in expression and breast cancer outcomes have been established, while CXCR4 and CXCR7 showed an opposite pattern in cancer as compared with normal and further differences between hormone receptor status and molecular subtypes (Zhao et al., 2014).
Entity Other malignancies
Note The importance of CXCL12 pathways in the proliferation, growth and metastasis processes has been assessed for many other types of tumors, among which prostate cancer (Vaday et. al., 2004; Zhang et al., 2008; Sun et al., 2010; Duda et al., 2011), pancreatic adenocarcinoma (Shen et al., 2013; Wu et al., 2013), neuroblastoma (Zagozdzon et al.,2008; Liberman et al., 2012), glioblastoma (Gatti et al., 2013; Wurth et al., 2014; Yao et al., 2015), colorectal cancer (Brand et al., 2005; Akishima-Fukasawa et al., 2009; Drury et al., 2010), melanoma (Scala et al., 2005; Toyozawa et al.,2012; Mitchell et al., 2014), bladder cancer (Retz et al., 2005; Shen et al., 2013), esophageal cancer (Sasaki et al., 2008; Wang et al., 2009; Tachezy et al., 2013), renal cancer (Pan et al., 2006; Ieran et al., 2014) and ovarian cancer (Popple et al., 2012).
Entity Human Immunodeficiency Virus-type 1 (HIV-1) infection
Note Since the discovery of the leukocyte-derived seven-transmembrane domain receptor (LESTR) twenty years ago (Loetscher et al., 1994) and of its function of co-receptor (termed fusin) for lymphocyte-tropic HIV-1 strains, the role of this chemokine receptor in modulating cell permissiveness to the infection was delineated in few years(Feng et al., 1996). At the same time, was reported the identification of the SDF-1 human chemokine as the natural ligand for LESTR/fusin protein, so named CXCR4, and its function of infection inhibitor by lymphocyte-tropic HIV-1 strains (Bleul et al., 1996 ; Oberlin et al., 1996). It was clarified that the HIV-1 infection requires expression of CD4, as primary receptor, and the CXCR4 as entry co-factor at the target cell surface; the engagement of these receptors by the HIV-1 envelope glycoprotein is essential for membrane fusion and, HIV infection can be prevented by HIV co-receptor antagonists (Davis et al., 1997). The HIV suppressive activity of SDF-1, by inhibition of HIV replication, was explained by a SDF-1 alpha-dependent internalization of the CXCR4 (Amara et al., 1997). Furthermore, as previously described in the mutations section, the SDF-1-beta chemokine gene variant in the homozygous state (SDF1-3'A/3'A), has been correlate to a delay of the AIDS onset (Winkler et al., 1998). During these years, different CXCR4 antagonists have reached later stage clinical trials but no one is currently underway (Henrich and Kuritzkes, 2013).
Entity WHIM Syndrome
Note WHIM is an acronym for an immunodeficiency disorder characterized by (w)arts, (h)ypogammaglobulinemia, (i)nfections and (m)yelokathexis symptoms. In most cases, it is caused by an inherited mutation affecting the CXCR4 gene (Hernandez et al., 2003; Liu et al., 2012).
Entity Autoimmune Diseases
Note CXCL12 functions as an anti-inflammatory chemokine during autoimmune inflammatory responses suggesting the use of CXCL12-based therapies for autoimmune inflammatory diseases (Karin, 2010; Villalvilla et al., 2014).


Calcium mobilization triggered by the chemokine CXCL12 regulates migration in wounded intestinal epithelial monolayers
Agle KA, Vongsa RA, Dwinell MB
J Biol Chem 2010 May 21;285(21):16066-75
PMID 20348095
Prognostic significance of CXCL12 expression in patients with colorectal carcinoma
Akishima-Fukasawa Y, Nakanishi Y, Ino Y, Moriya Y, Kanai Y, Hirohashi S
Am J Clin Pathol 2009 Aug;132(2):202-10; quiz 307
PMID 19605814
Molecular characterization of the tumor microenvironment in breast cancer
Allinen M, Beroukhim R, Cai L, Brennan C, Lahti-Domenici J, Huang H, Porter D, Hu M, Chin L, Richardson A, Schnitt S, Sellers WR, Polyak K
Cancer Cell 2004 Jul;6(1):17-32
PMID 15261139
HIV coreceptor downregulation as antiviral principle: SDF-1alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication
Amara A, Gall SL, Schwartz O, Salamero J, Montes M, Loetscher P, Baggiolini M, Virelizier JL, Arenzana-Seisdedos F
J Exp Med 1997 Jul 7;186(1):139-46
PMID 9207008
The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry
Bleul CC, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, Springer TA
Nature 1996 Aug 29;382(6594):829-33
PMID 8752280
CXCR4 and CXCL12 are inversely expressed in colorectal cancer cells and modulate cancer cell migration, invasion and MMP-9 activation
Brand S, Dambacher J, Beigel F, Olszak T, Diebold J, Otte JM, Göke B, Eichhorst ST
Exp Cell Res 2005 Oct 15;310(1):117-30
PMID 16125170
CXCR4/CXCL12 in non-small-cell lung cancer metastasis to the brain
Cavallaro S
Int J Mol Sci 2013 Jan 15;14(1):1713-27
PMID 23322021
CXCR4, but not CXCR7, discriminates metastatic behavior in non-small cell lung cancer cells
Choi YH, Burdick MD, Strieter BA, Mehrad B, Strieter RM
Mol Cancer Res 2014 Jan;12(1):38-47
PMID 24025971
Signal transduction due to HIV-1 envelope interactions with chemokine receptors CXCR4 or CCR5
Davis CB, Dikic I, Unutmaz D, Hill CM, Arthos J, Siani MA, Thompson DA, Schlessinger J, Littman DR
J Exp Med 1997 Nov 17;186(10):1793-8
PMID 9362541
Differential processing of stromal-derived factor-1alpha and stromal-derived factor-1beta explains functional diversity
De La Luz Sierra M, Yang F, Narazaki M, Salvucci O, Davis D, Yarchoan R, Zhang HH, Fales H, Tosato G
Blood 2004 Apr 1;103(7):2452-9
PMID 14525775
Polymorphism and circulating levels of the chemokine CXCL12 in colorectal cancer patients
Dimberg J, Hugander A, Löfgren S, Wågsä D
Int J Mol Med 2007 Jan;19(1):11-5
PMID 17143542
CXCL12 chemokine expression and secretion regulates colorectal carcinoma cell anoikis through Bim-mediated intrinsic apoptosis
Drury LJ, Wendt MK, Dwinell MB
PLoS One 2010 Sep 22;5(9):e12895
PMID 20877573
A common stromal cell-derived factor-1 chemokine gene variant is associated with the early onset of type 1 diabetes
Dubois-Laforgue D, Hendel H, Caillat-Zucman S, Zagury JF, Winkler C, Boitard C, Timsit J
Diabetes 2001 May;50(5):1211-3
PMID 11334429
CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies? Clin Cancer Res
Duda DG, Kozin SV, Kirkpatrick ND, Xu L, Fukumura D, Jain RK
2011 Apr 15;17(8):2074-80 doi: 10
PMID 21349998
HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor
Feng Y, Broder CC, Kennedy PE, Berger EA
Science 1996 May 10;272(5263):872-7
PMID 8629022
Molecular phenotype of CXCL12beta 3'UTR G801A polymorphism (rs1801157) associated to HIV-1 disease progression
Garcia-Moruja C, Rueda P, Torres C, Alcamí J, Luque F, Caruz A
Curr HIV Res 2009 Jul;7(4):384-9
PMID 19601773
Inhibition of CXCL12/CXCR4 autocrine/paracrine loop reduces viability of human glioblastoma stem-like cells affecting self-renewal activity
Gatti M, Pattarozzi A, Bajetto A, Würth R, Daga A, Fiaschi P, Zona G, Florio T, Barbieri F
Toxicology 2013 Dec 15;314(2-3):209-20
PMID 24157575
Matrix metalloproteinase-1 produced by human CXCL12-stimulated natural killer cells
Goda S, Inoue H, Umehara H, Miyaji M, Nagano Y, Harakawa N, Imai H, Lee P, Macarthy JB, Ikeo T, Domae N, Shimizu Y, Iida J
Am J Pathol 2006 Aug;169(2):445-58
PMID 16877347
HIV-1 entry inhibitors: recent development and clinical use
Henrich TJ, Kuritzkes DR
Curr Opin Virol 2013 Feb;3(1):51-7
PMID 23290628
Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease
Hernandez PA, Gorlin RJ, Lukens JN, Taniuchi S, Bohinjec J, Francois F, Klotman ME, Diaz GA
Nat Genet 2003 May;34(1):70-4
PMID 12692554
Role of the CXCR4/CXCL12 signaling axis in breast cancer metastasis to the brain
Hinton CV, Avraham S, Avraham HK
Clin Exp Metastasis 2010 Feb;27(2):97-105
PMID 18814042
CXCR4 and CXCR7 transduce through mTOR in human renal cancer cells
Ieranò C, Santagata S, Napolitano M, Guardia F, Grimaldi A, Antignani E, Botti G, Consales C, Riccio A, Nanayakkara M, Barone MV, Caraglia M, Scala S
Cell Death Dis 2014 Jul 3;5:e1310
PMID 24991762
Clinicopathological and therapeutic significance of CXCL12 expression in lung cancer
Imai H, Sunaga N, Shimizu Y, Kakegawa S, Shimizu K, Sano T, Ishizuka T, Oyama T, Saito R, Minna JD, Mori M
Int J Immunopathol Pharmacol 2010 Jan-Mar;23(1):153-64
PMID 20378003
The multiple faces of CXCL12 (SDF-1alpha) in the regulation of immunity during health and disease
Karin N
J Leukoc Biol 2010 Sep;88(3):463-73
PMID 20501749
The chemokine CXCL12 promotes survival of postmitotic neurons by regulating Rb protein
Khan MZ, Brandimarti R, Shimizu S, Nicolai J, Crowe E, Meucci O
Cell Death Differ 2008 Oct;15(10):1663-72
PMID 18583990
CXCR4 chemokine receptor signaling induces apoptosis in acute myeloid leukemia cells via regulation of the Bcl-2 family members Bcl-XL, Noxa, and Bak
Kremer KN, Peterson KL, Schneider PA, Meng XW, Dai H, Hess AD, Smith BD, Rodriguez-Ramirez C, Karp JE, Kaufmann SH, Hedin KE
J Biol Chem 2013 Aug 9;288(32):22899-914
PMID 23798675
Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis
Kryczek I, Wei S, Keller E, Liu R, Zou W
Am J Physiol Cell Physiol 2007 Mar;292(3):C987-95
PMID 16943240
Involvement of the CXCR7/CXCR4/CXCL12 axis in the malignant progression of human neuroblastoma
Liberman J, Sartelet H, Flahaut M, Mühlethaler-Mottet A, Coulon A, Nyalendo C, Vassal G, Joseph JM, Gross N
PLoS One 2012;7(8):e43665
PMID 22916293
WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4
Liu Q, Chen H, Ojode T, Gao X, Anaya-O'Brien S, Turner NA, Ulrick J, DeCastro R, Kelly C, Cardones AR, Gold SH, Hwang EI, Wechsler DS, Malech HL, Murphy PM, McDermott DH
Blood 2012 Jul 5;120(1):181-9
PMID 22596258
Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes
Loetscher M, Geiser T, O'Reilly T, Zwahlen R, Baggiolini M, Moser B
J Biol Chem 1994 Jan 7;269(1):232-7
PMID 8276799
Involvement of chemokine receptors in breast cancer metastasis
Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A
Nature 2001 Mar 1;410(6824):50-6
PMID 11242036
CXCL12 G801A polymorphism contributes to cancer susceptibility: a meta-analysis
Ma XY, Jin Y, Sun HM, Yu L, Bai J, Chen F, Fu SB
Cell Mol Biol (Noisy-le-grand) 2012 Jun 30;58 Suppl:OL1702-8
PMID 22762525
Protein expression of the chemokine receptor CXCR4 and its ligand CXCL12 in primary cutaneous melanoma--biomarkers of potential utility? Hum Pathol
Mitchell B, Leone D, Feller K, Menon S, Bondzie P, Yang S, Park HY, Mahalingam M
2014 Oct;45(10):2094-100 doi: 10
PMID 25130395
Haplotype analysis of the SDF-1 (CXCL12) gene in a longitudinal HIV-1/AIDS cohort study
Modi WS, Scott K, Goedert JJ, Vlahov D, Buchbinder S, Detels R, Donfield S, O'brien SJ, Winkler C
Genes Immun 2005 Dec;6(8):691-8
PMID 16177829
The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1
Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier JL, Arenzana-Seisdedos F, Schwartz O, Heard JM, Clark-Lewis I, Legler DF, Loetscher M, Baggiolini M, Moser B
Nature 1996 Aug 29;382(6594):833-5
PMID 8752281
Stromal derived factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis
Pan J, Mestas J, Burdick MD, Phillips RJ, Thomas GV, Reckamp K, Belperio JA, Strieter RM
Mol Cancer 2006 Nov 3;5:56
PMID 17083723
CXCR4 and CXCL12 immunoreactivities differentiate primary non-small-cell lung cancer with or without brain metastases
Paratore S, Banna GL, D'Arrigo M, Saita S, Iemmolo R, Lucenti L, Bellia D, Lipari H, Buscarino C, Cunsolo R, Cavallaro S
Cancer Biomark 2011-2012;10(2):79-89
PMID 22430135
The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis
Petit I, Jin D, Rafii S
Trends Immunol 2007 Jul;28(7):299-307
PMID 17560169
The chemokine, CXCL12, is an independent predictor of poor survival in ovarian cancer
Popple A, Durrant LG, Spendlove I, Rolland P, Scott IV, Deen S, Ramage JM
Br J Cancer 2012 Mar 27;106(7):1306-13
PMID 22415233
Beta-arrestin- but not G protein-mediated signaling by the "decoy" receptor CXCR7
Rajagopal S, Kim J, Ahn S, Craig S, Lam CM, Gerard NP, Gerard C, Lefkowitz RJ
Proc Natl Acad Sci U S A 2010 Jan 12;107(2):628-32
PMID 20018651
Secreted CXCL12 (SDF-1) forms dimers under physiological conditions
Ray P, Lewin SA, Mihalko LA, Lesher-Perez SC, Takayama S, Luker KE, Luker GD
Biochem J 2012 Mar 1;442(2):433-42
PMID 22142194
CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells
Retz MM, Sidhu SS, Blaveri E, Kerr SC, Dolganov GM, Lehmann J, Carroll P, Simko J, Waldman FM, Basbaum C
Int J Cancer 2005 Mar 20;114(2):182-9
PMID 15540205
CXCR7 impact on CXCL12 biology and disease
Sánchez-Martí L, Sánchez-Mateos P, Cabañas C
Trends Mol Med 2013 Jan;19(1):12-22
PMID 23153575
Expression of CXCL12 and its receptor CXCR4 correlates with lymph node metastasis in submucosal esophageal cancer
Sasaki K, Natsugoe S, Ishigami S, Matsumoto M, Okumura H, Setoyama T, Uchikado Y, Kita Y, Tamotsu K, Sakurai T, Owaki T, Aikou T
J Surg Oncol 2008 Apr 1;97(5):433-8
PMID 18176915
Expression of CXCR4 predicts poor prognosis in patients with malignant melanoma
Scala S, Ottaiano A, Ascierto PA, Cavalli M, Simeone E, Giuliano P, Napolitano M, Franco R, Botti G, Castello G
Clin Cancer Res 2005 Mar 1;11(5):1835-41
PMID 15756007
CXCL12-CXCR4 promotes proliferation and invasion of pancreatic cancer cells
Shen B, Zheng MQ, Lu JW, Jiang Q, Wang TH, Huang XE
Asian Pac J Cancer Prev 2013;14(9):5403-8
PMID 24175834
CXCR4-mediated Stat3 activation is essential for CXCL12-induced cell invasion in bladder cancer
Shen HB, Gu ZQ, Jian K, Qi J
Tumour Biol 2013 Jun;34(3):1839-45
PMID 23526079
CXCL12-G801A polymorphism modulates risk of colorectal cancer in Taiwan
Shi MD, Chen JH, Sung HT, Lee JS, Tsai LY, Lin HH
Arch Med Sci 2013 Dec 30;9(6):999-1005
PMID 24482642
CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression
Sun X, Cheng G, Hao M, Zheng J, Zhou X, Zhang J, Taichman RS, Pienta KJ, Wang J
Cancer Metastasis Rev 2010 Dec;29(4):709-22
PMID 20839032
CXCR7 expression in esophageal cancer
Tachezy M, Zander H, Gebauer F, von Loga K, Pantel K, Izbicki JR, Bockhorn M
J Transl Med 2013 Sep 30;11:238
PMID 24074251
CXCL12 (SDF-1)/CXCR4 pathway in cancer
Teicher BA, Fricker SP
Clin Cancer Res 2010 Jun 1;16(11):2927-31
PMID 20484021
Chemokine receptor CXCR4 is a novel marker for the progression of cutaneous malignant melanomas
Toyozawa S, Kaminaka C, Furukawa F, Nakamura Y, Matsunaka H, Yamamoto Y
Acta Histochem Cytochem 2012 Oct 31;45(5):293-9
PMID 23209338
CXCR4 and CXCL12 (SDF-1) in prostate cancer: inhibitory effects of human single chain Fv antibodies
Vaday GG, Hua SB, Peehl DM, Pauling MH, Lin YH, Zhu L, Lawrence DM, Foda HD, Zucker S
Clin Cancer Res 2004 Aug 15;10(16):5630-9
PMID 15328206
EnsemblCompara GeneTrees: Complete, duplication-aware phylogenetic trees in vertebrates
Vilella AJ, Severin J, Ureta-Vidal A, Heng L, Durbin R, Birney E
Genome Res 2009 Feb;19(2):327-35
PMID 19029536
SDF-1 signaling: a promising target in rheumatic diseases
Villalvilla A, Gomez R, Roman-Blas JA, Largo R, Herrero-Beaumont G
Expert Opin Ther Targets 2014 Sep;18(9):1077-87
PMID 24950016
G protein-coupled chemokine receptors induce both survival and apoptotic signaling pathways
Vlahakis SR, Villasis-Keever A, Gomez T, Vanegas M, Vlahakis N, Paya CV
J Immunol 2002 Nov 15;169(10):5546-54
PMID 12421931
CXCL12 modulation of CXCR4 and CXCR7 activity in human glioblastoma stem-like cells and regulation of the tumor microenvironment
Würth R, Bajetto A, Harrison JK, Barbieri F, Florio T
Front Cell Neurosci 2014 May 28;8:144
PMID 24904289
Expression of CXCL12/CXCR4 and its correlation to prognosis in esophageal squamous cell carcinoma
Wang DF, Lou N, Zeng CG, Zhang X, Chen FJ
Ai Zheng 2009 Feb;28(2):154-8
PMID 19550128
Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant
Winkler C, Modi W, Smith MW, Nelson GW, Wu X, Carrington M, Dean M, Honjo T, Tashiro K, Yabe D, Buchbinder S, Vittinghoff E, Goedert JJ, O'Brien TR, Jacobson LP, Detels R, Donfield S, Willoughby A, Gomperts E, Vlahov D, Phair J, O'Brien SJ
ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC) Science
PMID 9430590
Role of CXCL12/CXCR4 signaling axis in pancreatic cancer
Wu PF, Lu ZP, Cai BB, Tian L, Zou C, Jiang KR, Miao Y
Chin Med J (Engl) 2013;126(17):3371-4
PMID 24033967
CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma
Yao C, Li P, Song H, Song F, Qu Y, Ma X, Shi R, Wu J
Mol Neurobiol 2015 Jul 16
PMID 26179613
Identification and expression of novel isoforms of human stromal cell-derived factor 1
Yu L, Cecil J, Peng SB, Schrementi J, Kovacevic S, Paul D, Su EW, Wang J
Gene 2006 Jun 7;374:174-9
PMID 16626895
Csk homologous kinase inhibits CXCL12-CXCR4 signaling in neuroblastoma
Zagozdzon R, Fu Y, Avraham HK
Int J Oncol 2008 Mar;32(3):619-23
PMID 18292939
Chemokine CXCL12 and its receptor CXCR4 expression are associated with perineural invasion of prostate cancer
Zhang S, Qi L, Li M, Zhang D, Xu S, Wang N, Sun B
J Exp Clin Cancer Res 2008 Nov 4;27:62
PMID 18983683
A Comprehensive Analysis of CXCL12 Isoforms in Breast Cancer(1,2
Zhao S, Chang SL, Linderman JJ, Feng FY, Luker GD
) Transl Oncol
PMID 24836649
CXCL12 enhances human neural progenitor cell survival through a CXCR7- and CXCR4-mediated endocytotic signaling pathway
Zhu B, Xu D, Deng X, Chen Q, Huang Y, Peng H, Li Y, Jia B, Thoreson WB, Ding W, Ding J, Zhao L, Wang Y, Wavrin KL, Duan S, Zheng J
Stem Cells 2012 Nov;30(11):2571-83
PMID 22987307
Homeostatic chemokine receptors and organ-specific metastasis
Zlotnik A, Burkhardt AM, Homey B
Nat Rev Immunol 2011 Aug 25;11(9):597-606
PMID 21866172


This paper should be referenced as such :
Giulia Gentile, Maria Guarnaccia, Sebastiano Cavallaro
CXCL12 (chemokine (C-X-C motif) ligand 12)
Atlas Genet Cytogenet Oncol Haematol. 2016;20(5):256-263.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ]
  Chronic myelogenous leukaemia (CML)
Multiple Myeloma
Waldenstrom macroglobulinemia

External links

HGNC (Hugo)CXCL12   10672
Entrez_Gene (NCBI)CXCL12    C-X-C motif chemokine ligand 12
AliasesIRH; PBSF; SCYB12; SDF1; 
GeneCards (Weizmann)CXCL12
Ensembl hg19 (Hinxton)ENSG00000107562 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000107562 [Gene_View]  ENSG00000107562 [Sequence]  chr10:44377067-44385097 [Contig_View]  CXCL12 [Vega]
ICGC DataPortalENSG00000107562
TCGA cBioPortalCXCL12
AceView (NCBI)CXCL12
Genatlas (Paris)CXCL12
SOURCE (Princeton)CXCL12
Genetics Home Reference (NIH)CXCL12
Genomic and cartography
GoldenPath hg38 (UCSC)CXCL12  -     chr10:44377067-44385097 -  10q11.21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CXCL12  -     10q11.21   [Description]    (hg19-Feb_2009)
GoldenPathCXCL12 - 10q11.21 [CytoView hg19]  CXCL12 - 10q11.21 [CytoView hg38]
Genome Data Viewer NCBICXCL12 [Mapview hg19]  
OMIM600835   609423   
Gene and transcription
Genbank (Entrez)AI092156 AJ227905 AK090482 AK124641 AK292628
RefSeq transcript (Entrez)NM_000609 NM_001033886 NM_001178134 NM_001277990 NM_199168
Consensus coding sequences : CCDS (NCBI)CXCL12
Gene ExpressionCXCL12 [ NCBI-GEO ]   CXCL12 [ EBI - ARRAY_EXPRESS ]   CXCL12 [ SEEK ]   CXCL12 [ MEM ]
Gene Expression Viewer (FireBrowse)CXCL12 [ Firebrowse - Broad ]
GenevisibleExpression of CXCL12 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6387
GTEX Portal (Tissue expression)CXCL12
Human Protein AtlasENSG00000107562-CXCL12 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)CXCL12
Human Protein Atlas [tissue]ENSG00000107562-CXCL12 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:15:43 CEST 2021

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