PCDH17 Increases the Sensitivity of Colorectal Cancer to 5-Fluorouracil Treatment by Inducing Apoptosis and Autophagic Cell Death

Liu, Shuiping; Lin, Hui‐Ping; Ye, Yongling; Li, Qiang; Liu, Ying; Xie, Tian; Sui, Xinbing

doi:10.2139/ssrn.3416671

Cited by 4 publications

(2 citation statements)

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“…Autophagy serves as a metabolic mechanism in response to cellular stress to promote cell survival (Galati et al, 2019). However, it can also induce type II programmed cell death (Liu et al, 2019). Previous studies have shown that targeting autophagy using natural compounds may provide therapeutic benefits for cancers (Deng et al, 2019;Yang et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

TEOA Promotes Autophagic Cell Death via ROS-Mediated Inhibition of mTOR/p70S6k Signaling Pathway in Pancreatic Cancer Cells

Yang

et al. 2021

Front. Cell Dev. Biol.

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Pancreatic cancer is a common malignant tumor with high mortality, and novel therapeutic options have focused on ameliorating its poor prognosis. TEOA, a traditional Chinese herbal medicine, exhibits anti-inflammatory and anti-cancer activities. Our recent study has shown that TEOA inhibits proliferation and induces DNA damage in diffuse large B-cell lymphoma cells by activating the ROS-mediated p38 MAPK pathway. However, its effects on pancreatic cancer cells remain unknown. In the present study, we evaluated the effects of TEOA on the proliferation, migration of pancreatic cancer cells and explored the possible underlying mechanism of action. We found that TEOA significantly inhibited the proliferation and migration of pancreatic cancer cells in a time- and dose-dependent manner. Mechanistically, TEOA significantly induced mitochondrial dysfunction in PANC1 and SW1990 cells, as evidenced by the collapse of the mitochondrial membrane potential, exhausted ATP level, and excessive accumulation of intracellular ROS. Notably, our further experiments showed that TEOA induced autophagic cell death in pancreatic ductal adenocarcinoma cells by inactivating the ROS-dependent mTOR/p70S6k signaling pathway. More importantly, both pharmacological or genetic blocking of the autophagic flux signal could partly restore the cytotoxicity of TEOA, whereas activation of autophagy by rapamycin or EBSS induced starvation facilitated the cytotoxicity of TEOA. Concomitantly, N-acetylcysteine, a ROS scavenger, abolished the inhibition of the mTOR signaling pathway, thus preventing autophagy and restoring cell viability. Taken together, our results reveal that TEOA can lead to ROS-dependent autophagic cell death of pancreatic cancer cells by inducing mitochondrial dysfunction, which might be a promising therapeutic agent for pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

TEOA Promotes Autophagic Cell Death via ROS-Mediated Inhibition of mTOR/p70S6k Signaling Pathway in Pancreatic Cancer Cells

Yang

et al. 2021

Front. Cell Dev. Biol.

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“…Despite advancements in treatment strategies, the prognosis of patients with colorectal cancer remains poor, with a 5-year overall survival rate of ~40% (2). Several novel therapeutic approaches, such as aspirin-based chemoprevention and targeting cyclin-dependent kinase 4/tyrosine-protein kinase Fyn have improved the treatment efficacy (3)(4)(5). However, the molecular mechanism contributing to colorectal cancer progression remains elusive, making it difficult to develop therapeutic approaches for patients.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑934 promotes colorectal cancer cell proliferation by directly targeting Dickkopf‑related protein 2

Liu¹,

Ma²,

Zhang³

2021

Exp Ther Med

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Increasing evidence demonstrates that dysregulation of microRNAs (miRNAs/miRs) is implicated in the development of colorectal cancer. However, the biological functions of several differentially expressed miRNAs remain unknown. In the present study, a bioinformatic analysis of a previously published microarray data and reverse transcription-quantitative PCR analysis demonstrated that miR-934 expression was upregulated in colorectal cancer samples collected from patients. Mechanistically, Dickkopf-related protein 2 (DDK2) was identified as a novel target gene of miR-934 in colorectal cancer cells. Knockdown of DDK2 reversed the inactivation of Wnt signaling pathway induced using miR-934 inhibitor in colorectal cancer cells. In addition, DDK2 silencing reversed miR-934 inhibitor-induced cell proliferation inhibition and elevation of cell apoptosis. The results demonstrated that DDK2 mRNA expression was negatively associated with miR-934 expression in colorectal tumors. Collectively, the results of the present study demonstrated that the miR-934/DDK2 axis regulated colorectal cancer cell proliferation, suggesting that miR-934 may be a biomarker for patients with colorectal cancer.

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SFMBT1 facilitates colon cancer cell metastasis and drug resistance combined with HMG20A

Pan

et al. 2022

Cell Death Discov.

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In colorectal cancer (CRC), the development of reagents that increase sensitivity to chemotherapeutic agents could prevent drug resistance and improve patient survival. Scm-like with four malignant brain tumor domains 1 (SFMBT1) is up-regulated in CRC tumor tissues and cells and may be associated with drug resistance. We detected the expression of SFMBT1 in CRC tissue microarrays by immunohistochemistry. The role of SFMBT1 in the migration, proliferation and invasion of CRC or resistance to 5-fluorouracil (5-FU) was determined using scratch assay, colony formation and Transwell assay. Fluorescence co-localization and immunoprecipitation were used to analyze the correlation between SFMBT1 and high mobility group domain-containing protein 20 A (HMG20A). Xenograft experiments were conducted to investigate the role of SFMBT1 and HMG20A in tumor growth and metastasis in vivo. We found that SFMBT1 is up-regulated in CRC and its expression is further amplified in 5-FU resistance. SFMBT1 drives 5-FU resistance and CRC proliferation, migration and invasion. Correlation analysis shows that SFMBT1 and HMG20A are positively correlated. Mechanistically, fluorescence co-localization and immunoprecipitation assay indicate an interaction between SFMBT1 and HMG20A. Depletion of SFMBT1 down-regulates HMG20A downstream. These results were verified by murine xenograft and lung metastasis models. Our results indicate that the SFMBT1/HMG20A axis could be targeted to increase the resistance of CRC cells to 5-FU.

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PCDH17 Increases the Sensitivity of Colorectal Cancer to 5-Fluorouracil Treatment by Inducing Apoptosis and Autophagic Cell Death

Cited by 4 publications

References 0 publications

TEOA Promotes Autophagic Cell Death via ROS-Mediated Inhibition of mTOR/p70S6k Signaling Pathway in Pancreatic Cancer Cells

TEOA Promotes Autophagic Cell Death via ROS-Mediated Inhibition of mTOR/p70S6k Signaling Pathway in Pancreatic Cancer Cells

MicroRNA‑934 promotes colorectal cancer cell proliferation by directly targeting Dickkopf‑related protein 2

SFMBT1 facilitates colon cancer cell metastasis and drug resistance combined with HMG20A

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