SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer.
Colorectal cancer (CRC) is the third most common malignancies in adults. Similar to other solid tumors, CRC cells show increased proliferation and suppressed apoptosis during the development and progression of the disease. Previous studies have shown that a novel tumor oncogene, spermatogenic basic helix-loop-helix transcription factor zip 1 (SPZ1), can promote proliferation. However, it is unclear whether SPZ1 plays a role in suppressing apoptosis, and the molecular mechanism behind SPZ1's suppression of apoptosis in CRC remains unclear. Here, we found that silencing endogenous SPZ1 inhibits cell growth and induces apoptosis, and overexpression of SPZ1 promotes cell growth. These findings were corroborated by in vitro and in vivo studies. Interestingly, SPZ1 overexpressing cells were resistant to 5-fluorouracil, a drug commonly used to treat cancer. Moreover, knocking down SPZ1 led to the activation of caspase through the deregulation of Bim by ERK1/2, we found that CRC tissues had significantly higher SPZ1 and lower Bim expression, and SPZ1HBimL were associated with advanced clinical stage of CRC. Collectively, our findings demonstrate that SPZ1 contributes to tumor progression by limiting apoptosis. SPZ1 reduces apoptosis by altering the stability of Bim, suggesting SPZ1 may serve as a biomarker and therapeutic target for CRC.
['Liu|Xiao-Yu|XY|', 'Zheng|Chang-Bo|CB|', 'Wang|Teng|T|', 'Xu|Jian|J|', 'Zhang|Meng|M|', 'Gou|Ling-Shan|LS|', 'Jin|Linfang|L|', 'Qi|Xiaowei|X|', 'Zeng|Xianhai|X|', 'Li|Hongwen|H|', 'Qiu|Shuqi|S|', 'Zhang|Peng|P|']
D000818:Animals D017209:Apoptosis D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors D000072224:Bcl-2-Like Protein 11 D014408:Biomarkers, Tumor D045744:Cell Line, Tumor D049109:Cell Proliferation D015179:Colorectal Neoplasms D005472:Fluorouracil D015972:Gene Expression Regulation, Neoplastic D055785:Gene Knockdown Techniques D064593:Heterografts D006801:Humans D008819:Mice, Nude D019950:Mitogen-Activated Protein Kinase 1 D048052:Mitogen-Activated Protein Kinase 3 D009374:Neoplasms, Experimental D034741:RNA, Small Interfering D015854:Up-Regulation
SPZ1 Bim apoptosis colorectal cancer chemotherapy