- Volume 15 Issue 7
DOI QR Code
Pathological Implications of Cx43 Down-regulation in Human Colon Cancer
- Ismail, Rehana (Department of Biotechnology, University of Kashmir) ;
- Rashid, Rabiya (Department of Biotechnology, University of Kashmir) ;
- Andrabi, Khurshid (Department of Biotechnology, University of Kashmir) ;
- Parray, Fazl Q. (Department of Surgery, Sher-i-Kashmir Institute of Medical Sciences) ;
- Besina, Syed (Department of Pathology, Sher-i-Kashmir Institute of Medical Sciences) ;
- Shah, Mohd Amin (Department of clinical Biochemistry, Sher-i-Kashmir Institute of Medical Sciences) ;
- Hussain, Mahboob Ul (Department of Biotechnology, University of Kashmir)
- Published : 2014.04.01
Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (p<0.05) with the histological type and tumor invasion properties of the cancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer.
Gap-junctions;tumor suppressors;adenocarcinoma;connexin 43
- Ul-Hussain M, Zoidl G, Klooster J, et al (2008). IRES-mediated translation of the carboxy-terminal domain of the horizontal cell specific connexin Cx55.5 in vivo and in vitro. BMC Molecular Biology, 9, 52. https://doi.org/10.1186/1471-2199-9-52
- Sameer AS, Shah ZA, Syeed N, et al (2010). TP53 Pro47Ser and Arg72Pro polymorphisms and colorectal cancer predisposition in an ethnic Kashmiri population. Genet Mol Res, 13, 651-60.
- Plante I, Stewart MK, Barr K, Allan AL, Laird DW (2011). Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease. Oncogene, 30, 1681-92. https://doi.org/10.1038/onc.2010.551
- Sirnes S, Bruun J, Kolberg M, et al (2012). Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. Int J Cancer, 131, 570-81. https://doi.org/10.1002/ijc.26392
- Sohl G, Willecke K (2004). Gap junctions and the connexin protein family. Cardiovasc Res, 62, 228-32. https://doi.org/10.1016/j.cardiores.2003.11.013
- Solan JL, Hingorani SR, Lampe PD (2012). Changes in connexin43 expression and localization during pancreatic cancer progression. J Membr Biol, 245, 255-62. https://doi.org/10.1007/s00232-012-9446-2
- Yi ZC, Wang H, Zhang GY, Xia B (2007). Downregulation of connexin 43 in nasopharyngeal carcinoma cells is related to promoter methylation. Oral Oncol, 43, 898-904. https://doi.org/10.1016/j.oraloncology.2006.11.004
- Zhao JQ, Sun FJ, Liu SS, et al (2013). Expression of connexin 43 and E-cadherin protein and mRNA in non-small cell lung cancers in Chinese patients. Asian Pac J Cancer Prev, 14, 639-43. https://doi.org/10.7314/APJCP.2013.14.2.639
- Hatakeyama T, Dai P, Harada Y, et al (2013). Connexin43 functions as a novel interacting partner of heat shock cognate protein 70. Sci Rep, 3, 2719. https://doi.org/10.1038/srep02719
- Giepmans BN (2004). Gap junctions and connexin-interacting proteins. Cardiovasc Res, 62, 233-45. https://doi.org/10.1016/j.cardiores.2003.12.009
- Giepmans BN (2006). Role of connexin43-interacting proteins at gap junctions. Adv Cardiol, 42, 41-56.
- Greene FL (2002). The American joint committee on cancer: updating the strategies in cancer staging. Bull Am Coll Surg, 87, 13-5.
- Hu YQ, Liu YJ (2005). Expressions of Cx43 and Skp2 in epithelial ovarian tumor and their clinical significances. Ai Zheng, 24, 104-9.
- Javid G, Zargar SA, Rather S, et al (2011). Incidence of colorectal cancer in Kashmir valley, India. Indian J Gastroenterol, 30, 7-11. https://doi.org/10.1007/s12664-010-0071-7
- Kanczuga-Koda L, Sulkowski S, Koda M, et al (2004). Expression of connexins 26, 32 and 43 in the human colon--an immunohistochemical study. Folia Histochem Cytobiol, 42, 203-7.
- Kandouz M, Zhao J, Bier A, et al (2013). Post-transcriptional regulation of connexin43 in H-Ras-transformed cells. PLoS One, 8, 58500. https://doi.org/10.1371/journal.pone.0058500
- Khan NP, Pandith AA, Hussain MU, et al (2011). Novelty of Axin 2 and lack of Axin 1 gene mutation in colorectal cancer: a study in Kashmiri population. Mol Cell Biochem, 355, 149-55. https://doi.org/10.1007/s11010-011-0848-8
- Leithe E, Sirnes S, Omori Y, et al (2006). Downregulation of gap junctions in cancer cells. Crit Rev Oncogenesis, 12, 225-56. https://doi.org/10.1615/CritRevOncog.v12.i3-4.30
- Pandith AA, Siddiqi MA (2012). Burden of cancers in the valley of Kashmir: 5 year epidemiological study reveals a different scenario. Tumour Biol, 33, 1629-37. https://doi.org/10.1007/s13277-012-0418-z
- Benko G, Spajic B, Demirovic A, et al (2011). Prognostic value of connexin43 expression in patients with clinically localized prostate cancer. Prostate Cancer Prostatic Dis, 14, 90-5. https://doi.org/10.1038/pcan.2010.51
- Ableser MJ, Penuela S, Lee J, Shao Q, Laird DW (2013). Connexin43 reduces melanoma growth within a keratinocyte microenvironment and during tumorigenesis in vivo. J Biol Chem, 289, 1592-603
- Ahmad Waza A, Andrabi K, Ul Hussain M (2012). Adenosine-triphosphate-sensitive K(+)channel (Kir6.1): a novel phosphospecific interaction partner of connexin 43 (Cx43). Exp Cell Res, 318, 2559-66. https://doi.org/10.1016/j.yexcr.2012.08.004
- Araya R, Eckardt D, Maxeiner S, et al (2005). Expression of connexins during differentiation and regeneration of skeletal muscle: functional relevance of connexin43. J Cell Sci, 118, 27-37. https://doi.org/10.1242/jcs.01553
- Cruciani V, Mikalsen SO (2006). The vertebrate connexin family. Cell Mol Life Sci, 63, 1125-40. https://doi.org/10.1007/s00018-005-5571-8
- Dbouk HA, Mroue RM, El-Sabban ME, Talhouk RS (2009). Connexins: a myriad of functions extending beyond assembly of gap junction channels. Cell Commun Signal, 7, 4. https://doi.org/10.1186/1478-811X-7-4
- Dubina MV, Iatckii NA, Popov DE, et al (2002). Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancer. Oncogene, 21, 4992-96. https://doi.org/10.1038/sj.onc.1205630
- Gellhaus A, Wotzlaw C, Otto T, Fandrey J, Winterhager E (2010). More insights into the CCN3/Connexin43 interaction complex and its role for signaling. J Cell Biochem, 110, 129-40.
- Roles of connexins and pannexins in digestive homeostasis vol.72, pp.15, 2015, https://doi.org/10.1007/s00018-015-1961-8
- Connexin 43 expression is associated with poor survival in patients with esophageal squamous cell carcinoma vol.4, pp.6, 2016, https://doi.org/10.3892/mco.2016.828
- Connexins and their channels in inflammation vol.51, pp.6, 2016, https://doi.org/10.1080/10409238.2016.1204980