Tumor Biology

, Volume 37, Issue 5, pp 6501–6510 | Cite as

FAM172A is a tumor suppressor in colorectal carcinoma

Original Article


The present study was designed to elucidate the regulatory role of a novel protein FAM172A in carcinogenesis of colorectal carcinoma (CRC). Investigation of clinical samples using Western blotting showed that expression of FAM172A is significantly lower in cancerous tissues than in adjacent tissues. Furthermore, we constructed in vitro model for continuous overexpression and silencing of FAM172A with a retroviral vector system. FAM172A suppressed the proliferative and invasive potentials of LOVO cells as shown in MTT test, transwell migration assay, wound healing assay, 3D-culture morphologic study, and xenograft experiment. RT-PCR and Western blotting showed that FAM172A overexpression inhibited expressions of Cyclin D1, CDK2, MMP-2, MMP-9, PERK, elF2α, ATF6, XBP1, and GRP78, while FAM172A silencing induced their expressions. FAM172A might regulate ERS through PERK-elF2α, ATF6-XBP1-GRP78 signal pathway. The results implicated that FAM172A functioned as a tumor suppressor in colorectal carcinoma.


FAM172A Tumor suppressor Colorectal carcinoma 


Compliance with ethical standards

The protocol used in this study had been reviewed and approved by Medical Ethics Committee of Zhujiang Hospital, Southern Medical University. All participating patients were formally informed for the purpose of using their samples in this study, and a letter of consent had been signed by every patient participated.

Conflict of interest



  1. 1.
    Oh DY, Venook AP, Fong L. On the verge: immunotherapy for colorectal carcinoma. J Natl Compr Cancer Netw JNCCN. 2015;13:970–8.PubMedGoogle Scholar
  2. 2.
    Avital S, Kashtan H, Hadad R, Werbin N. Survival of colorectal carcinoma in the elderly. A prospective study of colorectal carcinoma and a five-year follow-up. Dis Colon Rectum. 1997;40:523–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet. 2010;375:1030–47.CrossRefPubMedGoogle Scholar
  4. 4.
    Rovcanin B, Ivanovski I, Djuric O, Nikolic D, Petrovic J, Ivanovski P. Mitotic crossover—an evolutionary rudiment which promotes carcinogenesis of colorectal carcinoma. World J Gastroenterol. 2014;20:12522–5.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med. 2009;361:2449–60.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Mehlen P, Fearon ER. Role of the dependence receptor DCC in colorectal cancer pathogenesis. J Clin Oncol Off J Am Soc Clin Oncol. 2004;22:3420–8.CrossRefGoogle Scholar
  7. 7.
    Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363:558–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. 2001;11:422–35.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Feng Z, Li H, Liu S, Cheng J, Xiang G, Zhang J. FAM172A induces S phase arrest of HepG2 cells via Notch 3. Oncol Rep. 2013;29:1154–60.PubMedGoogle Scholar
  10. 10.
    Li L, Dong X, Leong MC, Zhou W, Yang Z, Chen F, et al. Identification of the novel protein FAM172A, and its up-regulation by high glucose in human aortic smooth muscle cells. Int J Mol Med. 2010;26:483–90.PubMedGoogle Scholar
  11. 11.
    Patel D, Opriessnig T, Stein DA, Halbur PG, Meng XJ, Iversen PL, et al. Peptide-conjugated morpholino oligomers inhibit porcine reproductive and respiratory syndrome virus replication. Antivir Res. 2008;77:95–107.CrossRefPubMedGoogle Scholar
  12. 12.
    Patel D, Nan Y, Shen M, Ritthipichai K, Zhu X, Zhang YJ. Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation. J Virol. 2010;84:11045–55.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, CA) 2001;25:402-408.Google Scholar
  14. 14.
    Nan Y, Wang R, Shen M, Faaberg KS, Samal SK, Zhang YJ. Induction of type I interferons by a novel porcine reproductive and respiratory syndrome virus isolate. Virology. 2012;432:261–70.CrossRefPubMedGoogle Scholar
  15. 15.
    Jin HY, Qiu XG, Yang B. The microRNA3686 inhibits the proliferation of pancreas carcinoma cell line by targeting the polo-like kinase 1. BioMed Res Int. 2015;2015:954870.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Marshall J. Transwell(®) invasion assays. Methods Mol Biol. 2011;769:97–110.CrossRefPubMedGoogle Scholar
  17. 17.
    McGarry Houghton A: Matrix metalloproteinases in destructive lung disease. Matrix biology : Journal of the International Society for Matrix Biology 2015.Google Scholar
  18. 18.
    Brinckerhoff CE, Matrisian LM. Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev. 2002;3:207–14.CrossRefGoogle Scholar
  19. 19.
    Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S. Matrix metalloproteinases and gastrointestinal cancers: impacts of dietary antioxidants. World J Biol Chem. 2014;5:355–76.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Li LX, Tao Z, Dong XH, Liang WC, Yang ZH, Mou B, et al. [Molecular cloning of a novel gene, C5orf21 gene and its roles in diabetic macroangiopathy]. Zhonghua Yi Xue Za Zhi. 2009;89:2574–7.PubMedGoogle Scholar
  21. 21.
    Withers DA, Harvey RC, Faust JB, Melnyk O, Carey K, Meeker TC. Characterization of a candidate bcl-1 gene. Mol Cell Biol. 1991;11:4846–53.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Inaba T, Matsushime H, Valentine M, Roussel MF, Sherr CJ, Look AT. Genomic organization, chromosomal localization, and independent expression of human cyclin D genes. Genomics. 1992;13:565–74.CrossRefPubMedGoogle Scholar
  23. 23.
    He Y, Liu Z, Qiao C, Xu M, Yu J, Li G. Expression and significance of Wnt signaling components and their target genes in breast carcinoma. Mol Med Rep. 2014;9:137–43.PubMedGoogle Scholar
  24. 24.
    Hughes BT, Sidorova J, Swanger J, Monnat Jr RJ, Clurman BE. Essential role for Cdk2 inhibitory phosphorylation during replication stress revealed by a human Cdk2 knockin mutation. Proc Natl Acad Sci U S A. 2013;110:8954–9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lane ME, Yu B, Rice A, Lipson KE, Liang C, Sun L, et al. A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells. Cancer Res. 2001;61:6170–7.PubMedGoogle Scholar
  26. 26.
    Chen A, Xu J, Johnson AC. Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene. 2006;25:278–87.PubMedGoogle Scholar
  27. 27.
    Van Lint P, Libert C. Chemokine and cytokine processing by matrix metalloproteinases and its effect on leukocyte migration and inflammation. J Leukoc Biol. 2007;82:1375–81.CrossRefPubMedGoogle Scholar
  28. 28.
    Zucker S, Vacirca J. Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev. 2004;23:101–17.CrossRefPubMedGoogle Scholar
  29. 29.
    Wong JC, Chan SK, Schaeffer DF, Sagaert X, Lim HJ, Kennecke H, et al. Absence of MMP2 expression correlates with poor clinical outcomes in rectal cancer, and is distinct from MMP1-related outcomes in colon cancer. Clin Cancer Res. 2011;17:4167–76.CrossRefPubMedGoogle Scholar
  30. 30.
    Kim HC, Kim YS, Oh HW, Kim K, Oh SS, Kim JT, et al. Collagen triple helix repeat containing 1 (CTHRC1) acts via ERK-dependent induction of MMP9 to promote invasion of colorectal cancer cells. Oncotarget. 2014;5:519–29.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Clarke HJ, Chambers JE, Liniker E, Marciniak SJ. Endoplasmic reticulum stress in malignancy. Cancer Cell. 2014;25:563–73.CrossRefPubMedGoogle Scholar
  32. 32.
    Huber AL, Lebeau J, Guillaumot P, Petrilli V, Malek M, Chilloux J, et al. p58(IPK)-mediated attenuation of the proapoptotic PERK-CHOP pathway allows malignant progression upon low glucose. Mol Cell. 2013;49:1049–59.CrossRefPubMedGoogle Scholar
  33. 33.
    Tsaytler P, Harding HP, Ron D, Bertolotti A. Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science. 2011;332:91–4.CrossRefPubMedGoogle Scholar
  34. 34.
    Schindler AJ, Schekman R. In vitro reconstitution of ER-stress induced ATF6 transport in COPII vesicles. Proc Natl Acad Sci U S A. 2009;106:17775–80.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, et al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell. 2000;6:1355–64.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of General Surgery, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina
  2. 2.Department of Ophthalmology, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina
  3. 3.Department of Vascular Surgery, Nanfang HospitalSouthern Medical UniversityGuangzhouChina

Personalised recommendations