CD147 modulates autophagy through the PI3K/Akt/mTOR pathway in human prostate cancer PC-3 cells

Fang,Fang; Wang,Liuhang; Zhang,Shufang; Fang,Qing; Hao,Feng; Sun,Yanmei; Zhao,Liangzhong; Chen,Shuang; Liao,Huijuan; Wang,Liguo

doi:10.3892/ol.2015.2849

March-2015 Volume 9 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

March-2015 Volume 9 Issue 3

Full Size Image

Article

CD147 modulates autophagy through the PI3K/Akt/mTOR pathway in human prostate cancer PC-3 cells

Authors:
- Fang Fang
- Liuhang Wang
- Shufang Zhang
- Qing Fang
- Feng Hao
- Yanmei Sun
- Liangzhong Zhao
- Shuang Chen
- Huijuan Liao
- Liguo Wang
View Affiliations / Copyright

Affiliations: Department of Immunology, Jilin Medical College, Jilin, Jilin 132013, P.R. China, Department of Biochemistry, Changchun Medical College, Changchun, Jilin 130021, P.R. China, Department of Biochemistry, Jilin Medical College, Jilin, Jilin 132013, P.R. China, Department of Urology, Affiliated Hospital of Jilin Medical College, Jilin, Jilin 132011, P.R. China
Pages: 1439-1443
|
Published online on: January 5, 2015

https://doi.org/10.3892/ol.2015.2849
Expand metrics +

Abstract

The multifunctional glycoprotein cluster of differentiation (CD)147 is highly expressed on the cell surface of the majority of cancer cells, and promotes tumor invasion, metastasis and growth. However, the role of CD147 in autophagy has not yet been explored in prostrate cancer cells. In the present study, prostate cancer PC‑3 cells were cultured under starvation conditions, and the expression level of CD147 gradually increased. Therefore, RNA interference was used to inhibit CD147 expression, in order to investigate the biological role of this glycoprotein in autophagy progression. Autophagic activity was monitored by the changes in green fluorescent protein‑light chain 3 (GFP‑LC3) location and the expression of the autophagy‑associated protein LC3‑II. It was found that downregulation of CD147 significantly promoted GFP‑LC3 puncta formation and the expression of LC3‑II. Furthermore, the levels of phosphorylated serine/threonine protein kinase B (p‑Akt) and phosphorylated mammalian target of rapamycin (p‑mTOR) were significantly decreased, and the level of LC3‑II was inversely associated with levels of p‑Akt and p‑mTOR in cells with downregulated expression of CD147. The results of a trypan blue exclusion assay revealed that starvation‑induced cell death was increased in PC‑3/shCD147 cells compared with control PC‑3/Scramble cells (37.7±6.4 vs. 21.7±5.5%). Together, these results indicate that CD147 may be important in the inhibition of autophagy via the PI3K/Akt/mTOR pathway, which prevents cell death from unrestrained autophagy.

View Figures

View References

1	Ryter SW, Cloonan SM and Choi AM: Autophagy. A critical regulator of cellular metabolism and homeostasis. Mol Cells. 36:7–16. 2013. View Article : Google Scholar : PubMed/NCBI
2	Qu X, Zou Z, Sun Q, et al: Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell. 128:931–946. 2007. View Article : Google Scholar : PubMed/NCBI
3	Takagi H, Matsui Y and Sadoshima J: The role of autophagy in mediating cell survival and death during ischemia and reperfusion in the heart. Antioxid Redox Signal. 9:1373–1381. 2007. View Article : Google Scholar : PubMed/NCBI
4	Gozuacik D and Kimchi A: Autophagy as a cell death and tumor suppressor mechanism. Oncogene. 23:2891–2906. 2004. View Article : Google Scholar : PubMed/NCBI
5	Eisenberg-Lerner A, Bialik S, Simon HU and Kimchi A: Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ. 16:966–975. 2009. View Article : Google Scholar : PubMed/NCBI
6	Takeuchi H, Kondo Y, Fujiwara K, et al: Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors. Cancer Res. 65:3336–3346. 2005.PubMed/NCBI
7	Bi XC, Liu JM, Zheng XG, et al: Over-expression of extracellular matrix metalloproteinase inducer in prostate cancer is associated with high risk of prostate-specific antigen relapse after radical prostatectomy. Clin Invest Med. 34:E3582011.PubMed/NCBI
8	Yang JM, O’Neill P, Jin W, et al: Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim. J Biol Chem. 281:9719–9727. 2006. View Article : Google Scholar : PubMed/NCBI
9	Chen Y, Zhang H, Gou X, et al: Upregulation of HAb18G/CD147 in activated human umbilical vein endothelial cells enhances the angiogenesis. Cancer Lett. 278:113–121. 2009. View Article : Google Scholar : PubMed/NCBI
10	Dai JY, Dou KF, Wang CH, et al: The interaction of HAb18G/CD147 with integrin alpha6beta1 and its implications for the invasion potential of human hepatoma cells. BMC Cancer. 9:3372009. View Article : Google Scholar : PubMed/NCBI
11	Le Floch R, Chiche J, Marchig I, et al: CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors. Porc Natl Acad Sci USA. 108:16663–16668. 2011. View Article : Google Scholar
12	Wang L, Wu G, Yu L, et al: Inhibition of CD147 expression reduces tumor cell invasion in human prostate cancer cell line via RNA interference. Cancer Biol Ther. 5:608–614. 2006. View Article : Google Scholar : PubMed/NCBI
13	Zhao S, Ma W, Zhang M, et al: High expression of CD147 and MMP-9 is correlated with poor prognosis of triple-negative breast cancer (TNBC) patients. Med Oncol. 30:3352013. View Article : Google Scholar
14	Sier CF, Zuidwijk K, Zijlmans HJ, et al: EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma. Int J Cancer. 118:2991–2998. 2006. View Article : Google Scholar : PubMed/NCBI
15	Shukla S, Maclennan GT, Hartman DJ, et al: Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int J Cancer. 121:1424–1432. 2007. View Article : Google Scholar : PubMed/NCBI
16	Martinet W, De Meyer GR, Herman AG and Kockx MM: Amino acid deprivation induces both apoptosis and autophagy in murine C2C12 muscle cells. Biotechnol Lett. 27:1157–1163. 2005. View Article : Google Scholar : PubMed/NCBI
17	Gwak HS, Kim TH, Jo GH, et al: Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. PloS One. 7:e474492012. View Article : Google Scholar : PubMed/NCBI
18	Qian W, Liu J, Jin J, et al: Arsenic trioxide induces not only apoptosis but also autophagic cell death in leukemia cell lines via upregulation of Beclin-1. Leuk Res. 31:329–339. 2007. View Article : Google Scholar
19	Kabeya Y, Mizushima N, Ueno T, et al: LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19:5720–5728. 2000. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

CD147 modulates autophagy through the PI3K/Akt/mTOR pathway in human prostate cancer PC-3 cells

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles