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Article Open Access

Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway

  • Authors:
    • Chan-Hun Jung
    • Eun Mi Kim
    • Jong Kuk Park
    • Sang-Gu Hwang
    • Sung-Kwon Moon
    • Wun-Jae Kim
    • Hong-Duck Um
  • View Affiliations / Copyright

    Affiliations: Division of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea, Department of Biotechnology, Chungju National University, Chungju, Chungbuk, Republic of Korea, Department of Urology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
    Copyright: © Jung et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 2109-2113
    |
    Published online on: April 3, 2013
       https://doi.org/10.3892/or.2013.2381
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Abstract

Bmal1 is a core factor in the regulation of circadian rhythms. Previous studies have shown that Bmal1 suppresses tumor growth in cell culture and animal models and is downregulated in certain types of cancer. The aim of the present study was to investigated whether Bmal1 influences the invasiveness of cancer cells. We demonstrated that knockdown of Bmal1 by RNA interference promoted cancer cell invasion, whereas its overexpression reduced cellular invasiveness. These effects were observed in lung cancer and glioma cells, and occurred regardless of p53 status. Therefore, it appears that Bmal1 suppresses the invasion of multiple cancer types in a p53-independent manner. Bmal1 knockdown-induced cancer cell invasion was accompanied by activation of the PI3K-Akt-MMP-2 pathway, and was prevented by inhibitors of PI3K, Akt or MMP-2. This suggests that Bmal1 suppresses cell invasion by blocking the PI3K-Akt-MMP-2 pathway. Since this invasion pathway is activated by the oncogene Bcl-w, we investigated whether Bmal1 affects the activity of Bcl-w. As expected, Bmal1 attenuated the ability of Bcl-w to promote MMP-2 accumulation and cell invasion, supporting the idea that Bmal1 antagonizes Bcl-w activity. Collectively, our data suggest that Bmal1 is a tumor suppressor, capable of suppressing cancer cell growth and invasiveness, and support the recent proposal that there is a tight molecular link between circadian rhythms and tumor formation/progression.
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1 

Friedl P and Alexander S: Cancer invasion and the microenvironment: plasticity and reciprocity. Cell. 147:992–1009. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Mohawk JA, Green CB and Takahashi JS: Central and peripheral circadian clocks in mammals. Annu Rev Neurosci. 35:445–462. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Takahashi JS, Hong HK, Ko CH and McDearmon EL: The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet. 9:764–775. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Rafnsson V, Tulinius H, Jónasson JG and Hrafnkelsson J: Risk of breast cancer in female flight attendants: a population-based study (Iceland). Cancer Causes Control. 12:95–101. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Viswanathan AN, Hankinson SE and Schernhammer ES: Night shift work and the risk of endometrial cancer. Cancer Res. 67:10618–10622. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Schernhammer ES, Kroenke CH, Laden F and Hankinson SE: Night work and risk of breast cancer. Epidemiology. 17:108–111. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Fu L and Lee CC: The circadian clock: pacemaker and tumour suppressor. Nat Rev Cancer. 3:350–361. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Dunlap JC: Molecular bases for circadian clocks. Cell. 96:271–290. 1999. View Article : Google Scholar : PubMed/NCBI

9 

Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U and Schibler U: The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell. 110:251–260. 2002. View Article : Google Scholar

10 

Sato TK, Panda S, Miraglia LJ, Reyes TM, Rudic RD, McNamara P, Naik KA, FitzGerald GA, Kay SA and Hogenesch JB: A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron. 43:527–537. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Gery S, Gombart AF, Yi WS, Koeffler C, Hofmann WK and Koeffler HP: Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia. Blood. 106:2827–2836. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Winter SL, Bosnoyan-Collins L, Pinnaduwage D and Andrulis IL: Expression of the circadian clock genes Per1 and Per2 in sporadic and familial breast tumors. Neoplasia. 9:797–800. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Yeh KT, Yang MY, Liu TC, Chen JC, Chan WL, Lin SF and Chang JG: Abnormal expression of period 1 (PER1) in endometrial carcinoma. J Pathol. 206:111–120. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Pogue-Geile KL, Lyons-Weiler J and Whitcomb DC: Molecular overlap of fly circadian rhythms and human pancreatic cancer. Cancer Lett. 243:55–57. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Fu L, Pelicano H, Liu J, Huang P and Lee C: The circadian gene period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell. 111:41–50. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Gery S, Komatsu N, Baldjyan L, Yu A, Koo D and Koeffler HP: The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells. Mol Cell. 22:375–382. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Hua H, Wang Y, Wan C, Liu Y, Zhu B, Wang X, Wang Z and Ding JM: Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice. Cancer Gene Ther. 14:815–818. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Oda A, Katayose Y, Yabuuchi S, Yamamoto K, Mizuma M, Shirasou S, Onogawa T, Ohtsuka H, Yoshida H, Hayashi H, Rikiyama T, Kim H, Choe Y, Kim K, Son H, Motoi F, Egawa S and Unno M: Clock gene mouse period2 overexpression inhibits growth of human pancreatic cancer cells and has synergistic effect with cisplatin. Anticancer Res. 29:1201–1209. 2009.PubMed/NCBI

19 

King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TD, Vitaterna MH, Kornhauser JM, Lowrey PL, Turek FW and Takahashi JS: Positional cloning of the mouse circadian clock gene. Cell. 89:641–653. 1997. View Article : Google Scholar : PubMed/NCBI

20 

Zeng ZL, Wu MW, Sun J, Sun YL, Cai YC, Huang YJ and Xian LJ: Effects of the biological clock gene Bmal1 on tumour growth and anti-cancer drug activity. J Biochem. 148:319–326. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Kim EM, Kim J, Park JK, Hwang SG, Kim WJ, Lee WJ, Kang SW and Um HD: Bcl-w promotes cell invasion by blocking the invasion-suppressing action of Bax. Cell Signal. 24:1163–1172. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Lehman TA, Bennett WP, Metcalf RA, Welsh JA, Ecker J, Modali RV, Ullrich S, Romano JW, Appella E, Testa JR, Gerwin BI and Harris CC: p53 mutations, ras mutations, and p53-heat shock 70 protein complexes in human lung carcinoma cell lines. Cancer Res. 51:4090–4096. 1991.PubMed/NCBI

23 

Soussi T, Dehouche K and Béroud C: p53 website and analysis of p53 gene mutations in human cancer: forging a link between epidemiology and carcinogenesis. Hum Mutat. 15:105–113. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Roberson RS, Kussick SJ, Vallieres E, Chen SY and Wu DY: Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res. 65:2795–2803. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Shukla S, Maclennan GT, Hartman DJ, Fu P, Resnick MI and Gupta S: Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int J Cancer. 121:1424–1432. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Bae IH, Park MJ, Yoon SH, Kang SW, Lee SS, Choi KM and Um HD: Bcl-w promotes gastric cancer cell invasion by inducing matrix metalloproteinase-2 expression via phosphoinositide 3-kinase, Akt, and Sp1. Cancer Res. 66:4991–4995. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Bae IH, Yoon SH, Lee SB, Park JK, Ho JN and Um HD: Signaling components involved in Bcl-w-induced migration of gastric cancer cells. Cancer Lett. 277:22–28. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Kong D and Yamori T: Advances in development of phosphatidylinositol 3-kinase inhibitors. Curr Med Chem. 16:2839–2854. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Cory S and Adams JM: The Bcl-2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2:647–656. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Lee HW, Lee SS, Lee SJ and Um HD: Bcl-w is expressed in a majority of infiltrative gastric adenocarcinomas and suppresses the cancer cell death by blocking stress-activated protein kinase/c-Jun NH2-terminal kinase activation. Cancer Res. 63:1093–1100. 2003.

31 

Hoelzinger DB, Mariani L, Weis J, Woyke T, Berens TJ, McDonough WS, Sloan A, Coons SW and Berens ME: Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia. 7:7–16. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Chen-Goodspeed M and Lee CC: Tumor suppression and circadian function. J Biol Rhythms. 22:291–298. 2007. View Article : Google Scholar

33 

Mazzoccoli G, Panza A, Valvano MR, Palumbo O, Carella M, Pazienza V, Biscaglia G, Tavano F, Di Sebastiano P, Andriulli A and Piepoli A: Clock gene expression levels and relationship with clinical and pathological features in colorectal cancer patients. Chronobiol Int. 28:841–851. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Muller PA, Vousden KH and Norman JC: p53 and its mutants in tumor cell migration and invasion. J Cell Biol. 192:209–218. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Jung C, Kim EM, Park JK, Hwang S, Moon S, Kim W and Um H: Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway. Oncol Rep 29: 2109-2113, 2013.
APA
Jung, C., Kim, E.M., Park, J.K., Hwang, S., Moon, S., Kim, W., & Um, H. (2013). Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway. Oncology Reports, 29, 2109-2113. https://doi.org/10.3892/or.2013.2381
MLA
Jung, C., Kim, E. M., Park, J. K., Hwang, S., Moon, S., Kim, W., Um, H."Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway". Oncology Reports 29.6 (2013): 2109-2113.
Chicago
Jung, C., Kim, E. M., Park, J. K., Hwang, S., Moon, S., Kim, W., Um, H."Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway". Oncology Reports 29, no. 6 (2013): 2109-2113. https://doi.org/10.3892/or.2013.2381
Copy and paste a formatted citation
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Spandidos Publications style
Jung C, Kim EM, Park JK, Hwang S, Moon S, Kim W and Um H: Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway. Oncol Rep 29: 2109-2113, 2013.
APA
Jung, C., Kim, E.M., Park, J.K., Hwang, S., Moon, S., Kim, W., & Um, H. (2013). Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway. Oncology Reports, 29, 2109-2113. https://doi.org/10.3892/or.2013.2381
MLA
Jung, C., Kim, E. M., Park, J. K., Hwang, S., Moon, S., Kim, W., Um, H."Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway". Oncology Reports 29.6 (2013): 2109-2113.
Chicago
Jung, C., Kim, E. M., Park, J. K., Hwang, S., Moon, S., Kim, W., Um, H."Bmal1 suppresses cancer cell invasion by blocking the phosphoinositide 3-kinase-Akt-MMP-2 signaling pathway". Oncology Reports 29, no. 6 (2013): 2109-2113. https://doi.org/10.3892/or.2013.2381
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