Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanoma-associated antigen-encoding (MAGE) genes are expressed in melanoma and other cancers but not in normal somatic cells. MAGE expression is associated with aggressive tumor growth, poor clinical outcome, and resistance to chemotherapy, but the mechanisms have not been completely elucidated. In this study, we show that downregulation of MAGE-C2 in A375 melanoma cells and low-passage cultures from human metastatic melanomas (MRA cells) results in increased apoptosis and decreased growth of tumor xenografts in athymic nude mice. Previously, we showed that MAGE-C2 binds KAP1, a scaffolding protein that regulates DNA repair. Phosphorylation of KAP1-Serine 824 (Ser824) by ataxia-telangiectasia-mutated (ATM) kinase is necessary for repair of DNA double-strand breaks (DSBs); now we show that MAGE-C2 knockdown reduces, whereas MAGE-C2 overexpression increases, ATM kinase-dependent phosphorylation of KAP1-Ser824. We demonstrate that MAGE-C2 increases co-precipitation of KAP1 with ATM and that binding of MAGE-C2 to KAP1 is necessary for increased KAP1-Ser824 phosphorylation. Furthermore, ectopic expression of MAGE-C2 enhances repair of I-SceI endonuclease-induced DSBs in U-2OS cells. As phosphorylation of KAP1-Ser824 facilitates relaxation of heterochromatin, which is necessary for DNA repair and cellular proliferation, our results suggest that MAGE-C2 can promote tumor growth by phosphorylation of KAP1-Ser824 and by enhancement of DNA damage repair.
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PMID:MAGE-C2 promotes growth and tumorigenicity of melanoma cells, phosphorylation of KAP1, and DNA damage repair. 2309 6

Melanoma-associated antigen family A (MAGE-A) is a family of cancer/testis antigens that are expressed in malignant tumors but not in normal tissues other than the testes. MAGE-A12 is a MAGE-A family gene whose tumorigenic function in cancer cells remains unclear. Searches of the Oncomine and NextBio databases revealed that malignant tumors show up-regulation of MAGE-A12 mRNA relative to corresponding normal tissue. In PPC1 primary prostatic carcinoma cells and in HCT116 colorectal cancer cells (wild type and p53-depleted), MAGE-A12 gene knockdown using siRNA or shRNA diminishes cancer cell proliferation as assessed by cellular ATP levels, cell counting, and clonogenic assays. FACS analyses of annexin V-PI staining and DNA content show that MAGE-A12 knockdown causes G2/M arrest and apoptosis. In tumor xenografts of HCT116 cells, conditional knockdown of MAGE-A12 suppresses tumor growth. The depletion of MAGE-A12 leads to the accumulation of tumor suppressor p21 in PPC1, HCT116, and p53-depleted HCT116 cells. Conversely, CDKN1A knockdown partially rescues the viability of PPC1 cells transfected with siRNA targeting MAGE-A12, while p21 overexpression leads to proliferation arrest in PPC-1 cells. Furthermore, exogenous MAGE-A12 expression promotes the ubiquitination of p21. Our findings reveal that MAGE-A12 plays crucial roles in p21 stability and tumor growth, suggesting that MAGE-A12 could provide a novel target for cancer treatment.
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PMID:Melanoma antigen A12 regulates cell cycle via tumor suppressor p21 expression. 2897 29

Melanoma-associated antigen A3 (MAGEA3), a member of the cancer-testis antigen (CTA) family, is aberrantly expressed in various cancer types. Accumulating evidence indicates that MAGEA3 plays a vital role in the pathogenesis and development of various cancers. However, the underlying mechanisms behind the tumor-promoting effect of MAGEA3 remain unclear, particularly in cervical cancer (CC). The present study investigated the effects of MAGEA3 on CC cell proliferation and apoptosis as well as the underlying molecular mechanism. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays were used to evaluate the effects of MAGE-A3 on proliferation, cell cycle, and apoptosis. Co-immunoprecipitation (Co-IP), dual-luciferase reporter, western blotting, and quantitative RT-PCR assays were performed to investigate the regulatory mechanisms of MAGEA3 in CC cells. Compared to the control, MAGE-A3 overexpression markedly promoted the proliferation of SiHa cells in vitro and in vivo, increased the proportion of cells in S phase, and suppressed apoptosis. However, MAGEA3 knockdown inhibited proliferation, blocked the cell cycle in G1 phase, and induced apoptosis in HeLa cells. Further mechanistic study revealed that MAGEA3 interacts with KAP1, thereby suppressing p53 transcriptional activity, thus suppressing p53-mediated regulation of the expression of genes involved in the cell cycle (p21, cyclin D1) and apoptosis (Bax, Bcl-2, and PUMA). Collectively, our results, both in vivo and in vitro, indicate that the expression of MAGEA3 contributes to CC cell proliferation and tumor growth and exerts tumor-promoting effects by regulating the KAP1/p53 signaling pathway.
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PMID:MAGEA3 promotes proliferation and suppresses apoptosis in cervical cancer cells by inhibiting the KAP1/p53 signaling pathway. 3277 21

Prostate cancer (PC) is the most common reproductive cancer in men and the third leading cause of cancer death among men worldwide. Recently targeted therapy showed a significant therapeutic effect on PC, whereas finding more PC therapeutic target is still urgently needed. Melanoma-associated antigen-encoding C2 (MAGE-C2/CT10), which have significant homology with the MAGE-C1/CT-7 gene, was known to be involved in the development of a variety of tumors. However, the role and mechanism of MAGE-C2/CT10 in prostate cancer remains unclear. Herein, we found the high levels of MAGE-C2/CT10 in highly metastatic prostate cancer. Our findings confirmed that the depletion of MAGE-C2/CT10 suppressed the growth of PC cells, and restrained PC cell migration and invasion in vitro. We noticed MAGE-C2/CT10 could stimulate c-Myc expression via FBP1, and further contributed to PC cell proliferation and motility. Performing in vivo assays, we demonstrated MAGE-C2/CT10 promoted tumor growth and metastasis of PC cells in mice. Collectively, we found the abnormal expression of MAGE-C2/CT10 in PC, and revealed the regulatory mechanism underlying MAGE-C2/CT10 promoting PC progression and metastasis.
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PMID:MAGE-C2/CT10 promotes growth and metastasis through upregulating c-Myc expression in prostate cancer. 3330 Nov 7