2017.01.04 최장현

Gastric Cancer 조기위암의 육안분류 진행위암의 보우만분류 http://www.cancer.go.kr/mbs/cancer/jsp/cancer/cancer.jsp?cancerSeq=3797&menuSeq=3810&viewType=all&id=cancer_020103000000 http://www.paik.ac.kr/sanggye/depa/204/disease.asp?p_seq=125&p_gub=DISE&gotopage=&v_cid=704

SOX9(Sry-related HMG box9) a. Normal epithelium b. Gastric carcinoma

SOX9(Sry-related HMG box9) w: weeks postinjection

Figure 1. SOX9 is upregulated in human gastric cancer Gastric Cancer Subtypes. CIN: Chromosomal instability EBV: Epstein-Barr virus GSI: Genomically stable MSI: Microsatellite instability TCGA(The Cancer Genome Atlas) ACRG(Asian Cancer Research Group) MSS: Microsatellite stability EMT: Epithelial-to- mesenchymal transition OS: Overall Survival DFS: Disease-Free Survival

Figure 2. Tumor suppressor phenotype induced by Sox9 and β-catenin knockdown PARP1: Poly [ADP-rebose] polymerase1 role in repair of single-stranded DNA breaks Caspase-3: Cysteine-ASPartic acid protease-3 role in the execution-phase of cell apoptosis Cip: CDK-interacting protein(cip1=p21, inhibition of cell cycle) BMI-1: target of SOX9 and regulator of p21cip, inhibition of senescence SA-β-Gal: senescence associated beta-galactosidase SYBR Primer: 0.2μmol/L cDNA: 20ng/well

Figure 2. Tumor suppressor phenotype induced by Sox9 and β-catenin knockdown

Figure 3. SOX9 is required for gCSC maintenance and tumor initiation capacity CD44, OCT4, BMI-1, CD133: Cancer Stem Cell Marker Tumor initiating control cells pLKO 1/14.299 sh1 1/349.217 sh2 1/670.407 Ki-67: cellular marker for proliferation

Figure 4. SOX9-β-catenin signaling axis in response to H Figure 4. SOX9-β-catenin signaling axis in response to H. pylori infection

Figure 4. SOX9-β-catenin signaling axis in response to H Figure 4. SOX9-β-catenin signaling axis in response to H. pylori infection 695, 742 strain: cagA+/vacAs1m1 904, 803 strain: cagA-/vacAs2m2 cagA: Cytotoxin-associated gene A vacA: Vacuolating cytotoxin A

Figure 4. SOX9-β-catenin signaling axis in response to H Figure 4. SOX9-β-catenin signaling axis in response to H. pylori infection

Figure 5. H. pylori activity is mediated by SOX9-β-catenin signaling HP+: H. pylori-infected HP- H. pylori- noninfected

Figure 5. H. pylori activity is mediated by SOX9-β-catenin signaling IL4: Interleukin 4, inducing stimulation of activated B-cell and T-cell proliferation IL6: Interleukin 6, mediator of fever and of the acute phase response IL1β: Interleukin 1β, leukocytic pyrogen TNFα: Tumor Necrosis Factor α

Figure 6. SOX9 modulates chemotherapy response Cisplatin: 10 μmol/L Cisplatin: 1 μmol/L Cisplatin: chemotherapy medication used to treat a number of cancers

Figure 6. SOX9 modulates chemotherapy response SOX9-overexpressing MKN45 MKN45

Summary SOX9 expression is consistently elevated in gastric cancer Tumor cells depend on SOX9 to survive and proliferate SOX9 acts downstream β-catenin in gastric cancer SOX9 elevation acts with canonical wnt signaling to drive gastric cancer progression