SEPT9 explained

Septin-9 is a protein that in humans is encoded by the SEPT9 gene.^{[1] [2] [3]}

Interactions

SEPT9 has been shown to interact with SEPT2^[4] and SEPT7.^[4]

Function

Along with AHNAK, eIF4E and S100A11, SEPT9 has been shown to be essential for pseudopod protrusion, tumor cell migration and invasion.^[5]

Clinical significance

The v2 region of the SEPT9 promoter has been shown to be methylated in colorectal cancer tissue compared with normal colonic mucosa.^[6] Using highly sensitive real time PCR assays, methylated SEPT9 was detected in the blood of colorectal cancer patients. This alternate methylation pattern in cancer samples is suggestive of an aberrant activation or repression of the gene compared to normal tissue samples.^{[7] [8]}

Testing to detect methylated SEPT9 is not indicated as a first option for colorectal cancer screening.^[9] It is similar in specificity and sensitivity to the stool guaiac test or fecal immune tests, and those tests should be used in preference.^[9] In cases when the physician aggressively has recommended a colonoscopy and the patient has declined that and these other tests, then this test has advantages over patients having no screening at all.^[9]

See also

• Hereditary neuralgic amyotrophy

Further reading

• Pellegrino JE, George RA, Biegel J, Farlow MR, Gardner K, Caress J, Brown MJ, Rebbeck TR, Bird TD, Chance PF . 6 . Hereditary neuralgic amyotrophy: evidence for genetic homogeneity and mapping to chromosome 17q25 . Human Genetics . 101 . 3 . 277–283 . December 1997 . 9439655 . 10.1007/s004390050629 . 20263885 .
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . 6 . Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 6 . 1 . 63–70 . February 1999 . 10231032 . 10.1093/dnares/6.1.63 . free .
• Medina M, Marinescu RC, Overhauser J, Kosik KS . Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome . Genomics . 63 . 2 . 157–164 . January 2000 . 10673328 . 10.1006/geno.1999.6090 .
• Kalikin LM, Sims HL, Petty EM . Genomic and expression analyses of alternatively spliced transcripts of the MLL septin-like fusion gene (MSF) that map to a 17q25 region of loss in breast and ovarian tumors . Genomics . 63 . 2 . 165–172 . January 2000 . 10673329 . 10.1006/geno.1999.6077 .
• Russell SE, McIlhatton MA, Burrows JF, Donaghy PG, Chanduloy S, Petty EM, Kalikin LM, Church SW, McIlroy S, Harkin DP, Keilty GW, Cranston AN, Weissenbach J, Hickey I, Johnston PG . 6 . Isolation and mapping of a human septin gene to a region on chromosome 17q, commonly deleted in sporadic epithelial ovarian tumors . Cancer Research . 60 . 17 . 4729–4734 . September 2000 . 10987277 .
• McIlhatton MA, Burrows JF, Donaghy PG, Chanduloy S, Johnston PG, Russell SE . Genomic organization, complex splicing pattern and expression of a human septin gene on chromosome 17q25.3 . Oncogene . 20 . 41 . 5930–5939 . September 2001 . 11593400 . 10.1038/sj.onc.1204752 . free .
• Yamamoto K, Shibata F, Yamaguchi M, Miura O . Fusion of MLL and MSF in adult de novo acute myelomonocytic leukemia (M4) with t(11;17)(q23;q25) . International Journal of Hematology . 75 . 5 . 503–507 . June 2002 . 12095151 . 10.1007/BF02982114 . 28022344 .
• Surka MC, Tsang CW, Trimble WS . The mammalian septin MSF localizes with microtubules and is required for completion of cytokinesis . Molecular Biology of the Cell . 13 . 10 . 3532–3545 . October 2002 . 12388755 . 129964 . 10.1091/mbc.E02-01-0042 .
• Nagata K, Kawajiri A, Matsui S, Takagishi M, Shiromizu T, Saitoh N, Izawa I, Kiyono T, Itoh TJ, Hotani H, Inagaki M . 6 . Filament formation of MSF-A, a mammalian septin, in human mammary epithelial cells depends on interactions with microtubules . The Journal of Biological Chemistry . 278 . 20 . 18538–18543 . May 2003 . 12626509 . 10.1074/jbc.M205246200 . free .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . 6 . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–12135 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . free . 2004PNAS..10112130B .
• Nagata K, Asano T, Nozawa Y, Inagaki M . Biochemical and cell biological analyses of a mammalian septin complex, Sept7/9b/11 . The Journal of Biological Chemistry . 279 . 53 . 55895–55904 . December 2004 . 15485874 . 10.1074/jbc.M406153200 . free .
• Scott M, Hyland PL, McGregor G, Hillan KJ, Russell SE, Hall PA . Multimodality expression profiling shows SEPT9 to be overexpressed in a wide range of human tumours . Oncogene . 24 . 29 . 4688–4700 . July 2005 . 15782116 . 10.1038/sj.onc.1208574 . free .
• Ito H, Iwamoto I, Morishita R, Nozawa Y, Narumiya S, Asano T, Nagata K . Possible role of Rho/Rhotekin signaling in mammalian septin organization . Oncogene . 24 . 47 . 7064–7072 . October 2005 . 16007136 . 10.1038/sj.onc.1208862 . free .
• Scott M, McCluggage WG, Hillan KJ, Hall PA, Russell SE . Altered patterns of transcription of the septin gene, SEPT9, in ovarian tumorigenesis . International Journal of Cancer . 118 . 5 . 1325–1329 . March 2006 . 16161048 . 10.1002/ijc.21486 . 37031210 . free .
• Kuhlenbäumer G, Hannibal MC, Nelis E, Schirmacher A, Verpoorten N, Meuleman J, Watts GD, De Vriendt E, Young P, Stögbauer F, Halfter H, Irobi J, Goossens D, Del-Favero J, Betz BG, Hor H, Kurlemann G, Bird TD, Airaksinen E, Mononen T, Serradell AP, Prats JM, Van Broeckhoven C, De Jonghe P, Timmerman V, Ringelstein EB, Chance PF . 6 . Mutations in SEPT9 cause hereditary neuralgic amyotrophy . Nature Genetics . 37 . 10 . 1044–1046 . October 2005 . 16186812 . 10.1038/ng1649 . 1756558 .

Notes and References

1. Osaka M, Rowley JD, Zeleznik-Le NJ . MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25) . Proceedings of the National Academy of Sciences of the United States of America . 96 . 11 . 6428–6433 . May 1999 . 10339604 . 26898 . 10.1073/pnas.96.11.6428 . free . 1999PNAS...96.6428O .
2. Taki T, Ohnishi H, Shinohara K, Sako M, Bessho F, Yanagisawa M, Hayashi Y . AF17q25, a putative septin family gene, fuses the MLL gene in acute myeloid leukemia with t(11;17)(q23;q25) . Cancer Research . 59 . 17 . 4261–4265 . September 1999 . 10485469 .
3. Web site: Entrez Gene: SEPT9 septin 9.
4. Surka MC, Tsang CW, Trimble WS . The mammalian septin MSF localizes with microtubules and is required for completion of cytokinesis . Molecular Biology of the Cell . 13 . 10 . 3532–3545 . October 2002 . 12388755 . 129964 . 10.1091/mbc.E02-01-0042 .
5. Shankar J, Messenberg A, Chan J, Underhill TM, Foster LJ, Nabi IR . Pseudopodial actin dynamics control epithelial-mesenchymal transition in metastatic cancer cells . Cancer Research . 70 . 9 . 3780–3790 . May 2010 . 20388789 . 10.1158/0008-5472.CAN-09-4439 . free .
6. Church TR, Wandell M, Lofton-Day C, Mongin SJ, Burger M, Payne SR, Castaños-Vélez E, Blumenstein BA, Rösch T, Osborn N, Snover D, Day RW, Ransohoff DF . 6 . Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer . Gut . 63 . 2 . 317–325 . February 2014 . 23408352 . 3913123 . 10.1136/gutjnl-2012-304149 .
7. Grützmann R, Molnar B, Pilarsky C, Habermann JK, Schlag PM, Saeger HD, Miehlke S, Stolz T, Model F, Roblick UJ, Bruch HP, Koch R, Liebenberg V, Devos T, Song X, Day RH, Sledziewski AZ, Lofton-Day C . 6 . Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay . PLOS ONE . 3 . 11 . e3759 . 2008 . 19018278 . 2582436 . 10.1371/journal.pone.0003759 . free . 2008PLoSO...3.3759G .
8. deVos T, Tetzner R, Model F, Weiss G, Schuster M, Distler J, Steiger KV, Grützmann R, Pilarsky C, Habermann JK, Fleshner PR, Oubre BM, Day R, Sledziewski AZ, Lofton-Day C . 6 . Circulating methylated SEPT9 DNA in plasma is a biomarker for colorectal cancer . Clinical Chemistry . 55 . 7 . 1337–1346 . July 2009 . 19406918 . 10.1373/clinchem.2008.115808 . free .
9. , which cites
   • Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA, Albrecht JK, Goldstein DB, McHutchison JG . 6 . Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus . Gastroenterology . 139 . 1 . 120–9.e18 . July 2010 . 20399780 . 10.1053/j.gastro.2010.04.013 .
   • Ahlquist DA, Taylor WR, Mahoney DW, Zou H, Domanico M, Thibodeau SN, Boardman LA, Berger BM, Lidgard GP . 6 . The stool DNA test is more accurate than the plasma septin 9 test in detecting colorectal neoplasia . Clinical Gastroenterology and Hepatology . 10 . 3 . 272–7.e1 . March 2012 . 22019796 . 3980432 . 10.1016/j.cgh.2011.10.008 .