The role of mucolipin-2 in prostate cancer progress and breast cancer chemotherapy

Ph.D. ; Cancer is the first cause of death in the world. There is about 90.5 million people diagnosed of cancer in 2015. It causes about 8.8 million deaths (15.7 of deaths). The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer and stomach cancer, while in females, the most common types are breast cancer, colorectal cancer, lung cancer and cervical cancer. ; In the first part of this thesis, I will describe the role of MCOLN2 in prostate cancer. Bioinformatic analysis found that the expressional level of MCOLN2 was higher in prostate cancer tissues than that in normal prostate epithelial cells. Patients with higher MCOLN2 expression tend to have poor overall survival rates. Western blot and qRT-PCR results showed that MCOLN2 expression was upregulated in prostate cancer cell lines PC-3 and DU145 when compared with benign prostate epithelial cell line BPH. Functional studies suggested that MCOLN2 facilitated growth, migration, and invasion of Pca cells in vitro and promoted tumor proliferation in vivo. Mechanistically, MCOLN2 increased IL-1β production and activates NF-κB signal pathway, resultant in nuclear translocation of the p65. Moreover, the regulation of MCOLN2 on IL-1β production was dependent on its lysosomal Ca²⁺ activity. ; The second part of this thesis will study the role of MCOLN2 in chemoresistant breast cancer cells MCF7/ADM. My results showed that the level of MCOLN2 expression was upregulated in the Adriamycin resistant breast cancer cell lines MCF7/ADM, and knockdown of MCOLN2 sensitized the cells to Adriamycin. Furthermore, knockdown of MCOLN2 significantly reduced the enhanced autophagic flux in the Adriamycin resistant cell lines. To further study the function of MCOLN2 in regulating Adriamycin resistant of MCF-7, we used the mCherry-GFP-LC3B tandem reporter assay and electron microscopic examination to test the autophagosomes/autolysosomes. The results showed that knockdown of MCOLN2 significantly decreased Adriamycin resistance and the number of ...