• Biomolecules & Therapeutics
• /
• v.27 no.6
• /
• pp.591-602
• /
• 2019

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.

• Parasites, Hosts and Diseases
• /
• v.59 no.6
• /
• pp.547-556
• /
• 2021

Our objective was to investigate whether inflammatory microenvironment induced by Trichomonas vaginalis infection can stimulate proliferation of prostate cancer (PCa) cells in vitro and in vivo mouse experiments. The production of CXCL1 and CCL2 increased when cells of the mouse PCa cells (TRAMP-C2 cell line) were infected with live T. vaginalis. T. vaginalis-conditioned medium (TCM) prepared from co-culture of PCa cells and T. vaginalis increased PCa cells migration, proliferation and invasion. The cytokine receptors (CXCR2, CCR2, gp130) were expressed higher on the PCa cells treated with TCM. Pretreatment of PCa cells with antibodies to these cytokine receptors significantly reduced the proliferation, mobility and invasiveness of PCa cells, indicating that TCM has its effect through cytokine-cytokine receptor signaling. In C57BL/6 mice, the prostates injected with T. vaginalis mixed PCa cells were larger than those injected with PCa cells alone after 4 weeks. Expression of epithelial-mesenchymal transition markers and cyclin D1 in the prostate tissue injected with T. vaginalis mixed PCa cells increased than those of PCa cells alone. Collectively, it was suggested that inflammatory reactions by T. vaginalis-stimulated PCa cells increase the proliferation and invasion of PCa cells through cytokine-cytokine receptor signaling pathways.

• Journal of Gastric Cancer
• /
• v.3 no.4
• /
• pp.182-185
• /
• 2003

Purpose: Preoperative staging of gastric cancer is crucial because the treatment modality and the prognosis depend upon the stage of gastric cancer. Current treatment modalities for early gastric cancer have focused on the quality of life. Endoscopic ultrasonography (EUS) and abdominal computed tomography (CT) are commonly used diagnostic tools to evaluate the invasiveness (T stage) of the primary tumor. The purpose of this paper is to evaluate the sensitivity and the specificity of preoperative EUS and CT in comparison with postoperative pathology. Materials and Methods: From October 2001 to October 2002, EUS and abdominal CT were performed simultaneously on 75 patients who underwent radical gastric surgery for the treatment of gastric cancer. Through analyzing the clinical T stage and the pathologic T stage, We evaluated the diagnostic sensitivities and specificities of endoscopic ultrasonography and abdominal computed tomography. Results: The male-to-female sex ratio was 1 : 0.6 (males: 47, females: 28). The mean age was 55.4 years in males (range: $28\~81$) and 54.4 years in females (range: $23\∼77$). The clinical T stage based on EUS included 22 T1mm, 7 T1sm, 22 T2, and 24 T3. The clinical T stage based on CT included 20 Tx, 23 T2, and 32 T3. The permanent pathologic report confirmed 23 T1mm, 10 T1sm, 17 T2, 24 T3, and 1 T4. The sensitivity and specificity of EUS were $84.2\%\;and\;94.7\%$, respectively. However, the sensitivity and specificity of abdominal CT were $53.3\%\;and\;77.0\%$, respectively. Conclusion: Our data suggest that EUS is a very useful diagnostic tool for evaluating the T stage of gastric cancer because EUS has higher specificity than abdominal CT. Therefore, EUS may have a significant role as a preoperative diagnostic modality in patients undergoing minimally invasive surgery.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.35 no.2
• /
• pp.74-82
• /
• 2009

In order to make successful oral cancer treatment, we need to understand about tumor biology and effective chemotherapeutic agents. To achieve these studies, it is necessary to develope a proper in-vivo model. Therefore the author will make try to develop more improved animal model of more applicable in various method of cancer study. In this study, the author induced in-vivo tumorigenesis in nude mice by $YD-10B_{mod}$ cell line used by YD-10B cell line originated from oral tongue squamous cell carcinoma and observed tumor formations and invasiveness of surrounding tissue, and found some results as follows : 1. The experimental group($YD-10B_{mod}$, subcutaneous injection) produced tumors 13 out of 15 mice, while the control group produced none of 5 mice. 2. The inoculation of $1{\times}10^6$cells/mouse produced tumors 3 out of 5 mice and inoculation of $1{\times}10^7$cells/mouse, $2{\times}10^7$cells/mouse produced tumors in every 5 mice. 3. In the histopathologic studies, the inoculation of $1{\times}10^6$cells/mouse group showed the characteristic features of well-differentiated squamous cell carcinoma and demarcated expansile growth, while the inoculation of $1{\times}10^7$cells/mouse, $2{\times}10^7$cells/mouse group showed the expansile growth with partial central necrosis and invasive growth to surrounding fat & connective tissue. These findings suggest that atopic xenograft of $YD-10B_{mod}$ cell line in nude mice has a improved productivity of tumors, produced tumors showed the characteristics feature of human tumor and invasive growth to surrounding tissue in histopathologic appearance. These atopic nude mouse model of tongue carcinoma might assist in studying oral cancer biology and effective choice of chemotherapeutic agents.

• Journal of Ginseng Research
• /
• v.45 no.1
• /
• pp.134-148
• /
• 2021

Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF-β1) and self-renewal in A549 cells is relatively unknown. Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

• Journal of Life Science
• /
• v.25 no.12
• /
• pp.1439-1444
• /
• 2015

Steroid receptor coactivators (SRC) are transcriptional coactivators. Among SRCs, SRC-3 is the most studied in relation to different types of tumors. However, the role of SRC-3 in early lung development and lung cancer has not been well studied. The expression profiles of SRC-3 showed that SRC-3 contributed to bronchial and alveolar development in embryonic lung development. SRC-3 was strongly expressed in Clara cells and type II alveolar cells during fetal lung development (E17.5- E18.5), and SRC-3 was expressed in both cell types in the adult lung. TTF-1 was expressed in the lungs of heterozygote SRC-3 mice and Clara cell-specific-CCSP-TAg tumor mice, along with SRC-3 expression. The expression of TTF-1 was localized at transformed Clara cells and multifocal adenocarcinomas in lung cancer mice. However, SRC-3 was not expressed in the multifocal adenocarcinomas, suggesting that SRC-3 might not be involved in the invasiveness of lung cancer. Cotransfection of TTF-1 in Clara cell-specific mtCC cell lines resulted in significant activation of CCSP expression. However, cotransfection of SRC-3 had no significant effects on transient transfection. These in vivo and in vitro results suggest that SRC-3 does not play a significant role in lung tumor progression. In conclusion, SRC-3 is involved in bronchial and alveolar development in fetal and adult lungs, but it does not play an important role in the progression of Clara cell-derived lung cancer.

• Journal of Gastric Cancer
• /
• v.4 no.4
• /
• pp.213-218
• /
• 2004

Purpose: The superficial spreading type of early gastric cancer has different clinicopathologic features from other types of early gastric cancer in terms of its invasiveness and lymph-node metastases. Therefore, we attempted to elucidate the pathological features, surgical procedures and patients prognoses. Materials and Methods: Clinical information was reviewed for patients who had undergone a gastrectomy for gastric cancer during an 8-year period ($1995\~2002$) at Dankook University Hospital and Ulsan University, with an average follow-up of 48 months. Three hundred (300) superficial spreading lesions were analyzed with respect to macroscopic type, lymph-node (LN) metastasis, recurrent pattern, survival rate and method of surgical operation. In addition, the clinicopathological features of the superficial spreading type were compared with those of 739 other patients with small-sized cancer. Results: In both groups, the IIc-type macroscopic lesion, the elevated subtype to be more specific, occurred most frequently. There was no significant difference in the method of surgery between the groups. The submucosal invasion was $39.8\%$ in small-sized cancer, and $61.7\%$ in superficial spreading cancer (P=0.005). The incidence of LN metastasis was $11.3\%$ in early gastric cancer, $7.8\%$ in small-sized cancer and $20.0\%$ in superficial spreading cancer (P=0.005). The incidence of lymphatic invasion was $4.6\%$ in small-sized cancer and $13.0\%$ in superficial spreading cancer (P=0.009). The incidence of recurrence was $1.4\%$ in small-sized cancer and $3.6\%$ in superficial spreading cancer. The overall 5-year survival rate was $84.8\%$ in superficial spreading cancer and $93.0\%$ in small-sized cancer (P=0.052). The 5-year diseasefree survival rate was $94.7\%$ in superficial spreading cancer and $87.5\%$ in small-sized cancer (P=0.053). Conclusion: The superficial spreading type of early gastric cancer tends to be more invasive and to show a higher incidence of lymph-node metastasis than small-sized early gastric cancer. A wide resection with extensive lymph-node dissection seems to be an appropriate treatment for a superficial spreading type of early gastric cancer.

• BMB Reports
• /
• v.48 no.11
• /
• pp.597-598
• /
• 2015

Mitochondrial respiratory defect is a key bioenergetics feature of hepatocellular carcinoma (HCC) cells. However, their involvement and roles in HCC development and progression remain unclear. Recently, we identified 10 common mitochondrial defect (CMD) signature genes that may be induced by retrograde signaling-mediated transcriptional reprogramming in response to HCC mitochondrial defects. HCC patients with enriched expression of these genes had poor prognostic outcomes, such as shorter periods of overall survival and recurrence-free survival. Nuclear protein 1 (NUPR1), a key transcription regulator, was up-regulated by Ca⁺⁺-mediated retrograde signaling. NUPR1-centric network analysis and a biochemical promoter-binding assay demonstrated that granulin (GRN) is a key downstream effector of NUPR1 for the regulation of HCC cell invasiveness; association analysis of the NUPR1-GRN pathway supported this conclusion. Mitochondrial respiratory defects and retrograde signaling thus play pivotal roles in HCC progression, highlighting the potential of the NUPR1-GRN axis as a novel diagnostic marker and therapeutic target for HCC.

• Molecules and Cells
• /
• v.42 no.7
• /
• pp.530-545
• /
• 2019

Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive $CD133^+/CD24^-$ cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.

• BMB Reports
• /
• v.52 no.5
• /
• pp.330-335
• /
• 2019

Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx.