High Expression of COL17A1 Predicts Poor Prognosis and Promotes the Tumor Progression via NF-κB Pathway in Pancreatic Adenocarcinoma

Mao, Feiyu; Li, Duguang; Xin, Zechang; Du, Yuchen; Wang, Xiaodong; Xu, Peng; Li, Zhennan; Qian, Jianjun; Yao, Jie

doi:10.1155/2020/8868245

Cited by 6 publications

(10 citation statements)

References 44 publications

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“…To examine the effects of COL17A1 expression on tumorigenesis in vivo, we established two murine homograft tumor models in which KPC or AK4.4 cells were injected subcutaneously into syngeneic C57BL/6 or FVB mice (C57BL/6‐KPC and FVB‐AK4.4 models), respectively (Figure 3A). KPC‐Col17a1 cells formed larger tumors than did KPC‐vector cells in recipient C57BL/6 mice (Figure 3B–D), consistent with a recent finding that COL17A1 expression promoted the growth of tumors formed by the human pancreatic cancer cell line AsPC‐1 in immunodeficient nude mice 14 . In contrast, tumors formed by AK4.4‐Col17a1 cells were markedly smaller than those formed by AK4.4‐vector cells in recipient FVB mice (Figure 3E–G).…”

Section: Resultssupporting

confidence: 91%

“…expression in tumor tissue was associated with overall survival in PAAD and BRCA (Figure 1A,C), consistent with previous observations, 14,16 although this association was not significant for BRCA after Bonferroni correction for multiple testing. Of note, a higher COL17A1 mRNA abundance was associated with a worse or better overall survival for patients with PAAD or BRCA, respectively, suggesting that COL17A1 may have different roles in cancer progression depending on cancer type.…”

Section: Survival Analysis For Cancer Patients Revealed That Col17a1supporting

confidence: 91%

“…The role of COL17A1 in cancer progression, however, appears to be complex 8 . Overexpression of COL17A1 in PAAD cells was found to promote cell proliferation in vitro and tumor growth in immunocompromised nude mice, whereas it was shown to inhibit the proliferation of invasive breast carcinoma (BRCA) cells 14–16 . Furthermore, whereas COL17A1 expression was found to promote cell invasion in colorectal cancer and squamous cell carcinoma, it suppressed cell migration and invasion in PAAD and BRCA 17–20 .…”

Section: Introductionmentioning

confidence: 99%

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Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment

Kashiwagi,

Funayama,

Aoki

et al. 2023

Cancer Science

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Expression of the gene for collagen XVII (COL17A1) in tumor tissue is positively or negatively associated with patient survival depending on cancer type. High COL17A1 expression is thus a favorable prognostic marker for breast cancer but unfavorable for pancreatic cancer. This study explored the effects of COL17A1 expression on pancreatic tumor growth and their underlying mechanisms. Analysis of published single‐cell RNA‐sequencing data for human pancreatic cancer tissue revealed that COL17A1 was expressed predominantly in cancer cells rather than surrounding stromal cells. Forced expression of COL17A1 did not substantially affect the proliferation rate of the mouse pancreatic cancer cell lines KPC and AK4.4 in vitro. However, in mouse homograft tumor models in which KPC or AK4.4 cells were injected into syngeneic C57BL/6 or FVB mice, respectively, COL17A1 expression promoted or suppressed tumor growth, respectively, suggesting that the effect of COL17A1 on tumor growth was influenced by the tumor microenvironment. RNA‐sequencing analysis of tumor tissue revealed effects of COL17A1 on gene expression profiles (including the expression of genes related to cell proliferation, the immune response, Wnt signaling, and Hippo signaling) that differed between C57BL/6‐KPC and FVB‐AK4.4 tumors. Our data thus suggest that COL17A1 promotes or suppresses cancer progression in a manner dependent on the interaction of tumor cells with the tumor microenvironment.

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Section: Resultssupporting

confidence: 91%

Section: Survival Analysis For Cancer Patients Revealed That Col17a1supporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment

Kashiwagi,

Funayama,

Aoki

et al. 2023

Cancer Science

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“…Dsg3 plays an oncogenic role in head neck cancer [53]. Col17a1 plays an essential role in many malignancies by contributing to cancer cell proliferation and invasion [54].…”

Section: Discussionmentioning

confidence: 99%

Expansion of mouse castration-resistant intermediate prostate stem cells in vitro

Zhou

et al. 2022

Stem Cell Res Ther

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Background Most castration-resistant prostate cancers (CRPCs) have a luminal phenotype with high androgen receptor (AR) and prostate-specific antigen (PSA) expression. Currently, it is difficult to culture castration-resistant luminal cells with AR and PSA expression. Methods We formulated a custom-made medium and isolated primary cells from the prostate of adult wild-type (WT) and TRAMP mice. The cells were characterized by immunofluorescence staining, transcriptomic analysis, and qRT-PCR verification. Their self-renewal and differentiation potential in vitro and in vivo were examined. We treated the cells with androgen deprivation and enzalutamide and performed immunofluorescence staining and western blotting to analyze their expression of AR and PSA. Results We isolated a novel type of castration-resistant intermediate prostate stem cells (CRIPSCs) from adult WT and TRAMP mice. The mouse CRIPSCs proliferated rapidly in two-dimensional (2D) culture dishes and can be cultured for more than six months. The mouse CRIPSCs expressed luminal markers (AR, PSA, and Dsg4), basal markers (CK5 and p63), Psca, and the intermediate cell marker (Ivl). Transcriptomic analysis showed that the mouse CRIPSCs had upregulated signaling pathways related to cancer development and drug resistance. In the long-term culture, TRAMP CRIPSCs had higher expression of the genes related to stem cells and cancers than WT mice. Both WT and TRAMP CRIPSCs formed organoids in Matrigel. WT CRIPSCs did not form prostate tissues when transplanted in vivo without urogenital sinus mesenchyme (UGM) cells. In contrast, TRAMP CRIPSCs formed prostate ducts in NOG mice without UGM cells and differentiated into luminal, basal, and neuroendocrine cells. Androgens regulated AR translocation between the nucleus and cytoplasm in the mouse CRIPSCs. Treatment of androgen deprivation (ADT) and enzalutamide reduced AR expression in WT and TRAMP CRIPSCs; however, this treatment promoted PSA expression in TRAMP, while not WT CRIPSCs, similar to the clinical observations of CRPC. Conclusions Our study established a method for isolating and expanding mouse CRIPSCs in 2D culture dishes. Mouse CRIPSCs had markers of basal and luminal cells, including AR and PSA, and can differentiate into prostate organoids and tissues. TRAMP CRIPSCs had elevated PSA expression upon ADT and enzalutamide treatment. Our method can be translated into clinical settings for CRPC precision medicine.

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“…XVII collagen is an adhesion protein present in basal epithelial cells, encoded by COL17A1, that affects the growth and migration of cells [ 29 ]. COL17A1 is associated with poor prognosis in several tumors [ 30 , 31 ]. Pulari et al found that high expression and hypomethylation of COL17A1 were associated with poor prognosis in epithelial carcinoma [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of ECT2 and COL17A1 as Potential Biomarkers for Pancreatic Cancer

Huang

et al. 2022

Disease Markers

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Background. Pancreatic cancer (PC) is a malignant tumor of the digestive tract. It presents with atypical clinical symptoms and lacks specific diagnostic indicators. This study is aimed at exploring the potential biomarkers of PC. Methods. TCGA database pancreatic cancer dataset was normalized and used to identify differentially expressed genes (DEGs). Survival, independent prognostic, and clinical correlation analyses were performed on DEGs to screen for key genes. DNA methylation, mutation, and copy number variation (CNV) analyses were used to analyze genetic variants in key genes. GSEA was performed to explore the functional enrichment of the key genes. Based on the expression of key genes, construction of a competing endogenous RNA (ceRNA) network, analysis of the tumor microenvironment (TME), and prediction of chemotherapeutic drug sensitivity were performed. Furthermore, the GEO database was used to validate the reliability of key genes. Results. Two key genes (ECT2 and COL17A1) were identified, which were highly expressed in PC. The mRNA expression of ECT2 and COL17A1 was associated with DNA methylation and CNV. The cell cycle, proteasome, and pathways in cancer were enriched in the high-COL17A1 and ECT2 groups. The TME results showed that immune scores were decreased in the high-ECT2 group. CeRNA network results showed that there were eleven miRNAs were involved in the regulation of ECT2 and COL17A1. Moreover, pRRophetic analysis showed that 20 chemotherapeutic drugs were associated with ECT2 and COL17A1 expression. Conclusions. Collectively, ECT2 and COL17A1 may be potential biomarkers for PC, providing a new direction for clinical diagnosis and treatment.

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High Expression of COL17A1 Predicts Poor Prognosis and Promotes the Tumor Progression via NF-κB Pathway in Pancreatic Adenocarcinoma

Cited by 6 publications

References 44 publications

Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment

Collagen XVII regulates tumor growth in pancreatic cancer through interaction with the tumor microenvironment

Expansion of mouse castration-resistant intermediate prostate stem cells in vitro

Integrated Analysis of ECT2 and COL17A1 as Potential Biomarkers for Pancreatic Cancer

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