CXCL3 overexpression promotes the tumorigenic potential of uterine cervical cancer cells via the MAPK/ERK pathway

Qi, Yaling; Li, Yue; Man, Xiaxia; Sui, Hongyu; Zhao, Xiao-Lian; Zhang, Pengxia; Qu, Xiusheng; Zhang, Hui; Wang, Baixin; Li, Jing; Qi, Shu-Fang; Liu, Jia; Luan, Hemi; Zhang, Chunbin; Wang, Weiqun

doi:10.1002/jcp.29353

Cited by 36 publications

(39 citation statements)

References 36 publications

(47 reference statements)

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“…CXCL3 is one of the five up-regulated genes shared between G12D and G12V mice. Recent study has shown that CXCL3 overexpression can promotes the tumorigenic potential of uterine cervical cancer cells via the MAPK/ERK pathway 40 , and can be a potential therapeutic target for breast cancer 41 . Thus, CXCL3 could be a downstream target of mutant Kras.…”

Section: Discussionmentioning

confidence: 99%

Differences in gynecologic tumor development in Amhr2-Cre mice with KRASG12D or KRASG12V mutations

Kun

Tsang

Lin

et al. 2020

Sci Rep

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How different KRAS variants impact tumor initiation and progression in vivo has not been thoroughly examined. We hypothesize that the ability of either KRASG12D or KRASG12V mutations to initiate tumor formation is context dependent. Amhr2-Cre mice express Cre recombinase in tissues that develop into the fallopian tubes, uterus, and ovaries. We used these mice to conditionally express either the KRASG12V/+or KRASG12D/+ mutation. Mice with the genotype Amhr2-Cre Pten(fl/fl) KrasG12D/+(G12D mice) had abnormal follicle structures and developed low-grade serous ovarian carcinomas with 100% penetrance within 18 weeks. In contrast, mice with the genotype Amhr2-Cre Pten(fl/fl) KrasG12V/+ (G12V mice) had normal follicle structures, and about 90% of them developed uterine tumors with diverse histological features resembling those of leiomyoma and leiomyosarcoma. Granulosa cell tumors also developed in G12V mice. Differences in cell-signaling pathways in the uterine tissues of G12D and G12V mice were identified using RNA sequencing and reverse-phase protein array analyses. We found that CTNNB1, IL1A, IL1B, TNF, TGFB1, APP, and IL6 had the higher activity in G12V mice than in G12D mice. These mouse models will be useful for studying the differences in signaling pathways driven by KrasG12V/+ or KrasG12D/+ mutations to aid development of targeted therapies for specific KRAS mutant variants. Our leiomyoma model driven by the KrasG12V/+ mutation will also be useful in deciphering the malignant progression from leiomyoma to leiomyosarcoma.

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Section: Discussionmentioning

confidence: 99%

Differences in gynecologic tumor development in Amhr2-Cre mice with KRASG12D or KRASG12V mutations

Kun

Tsang

Lin

et al. 2020

Sci Rep

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“…On the other hand, chemotherapy agents, including cisplatin, selectively inhibited regulatory and suppressor cells at low doses based on the previous study. 27 The results of our bioinformatics analysis showed that several anti-tumor chemokines [28][29] were identi ed to be enriched in the immunotype A group by bioinformatics analysis, while their role might be veiled by the coexistence of some pro-tumor molecules [30][31] . With the performance of ACT, the possibly diminished protumor feature might magnify the anti-tumor function in the microenvironment.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Immunoscore Signature Predicts Postoperative Survival and Adjuvant Chemotherapeutic Benefits in Esophageal Squamous Cell Carcinoma

Zhuge

Huang

Xie

et al. 2020

Preprint

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Objective: The aim of this study was to construct the immunoscore (IS) to facilitate the prediction of postoperative survival and benefit from adjuvant chemotherapy (ACT) in esophageal squamous cell carcinoma (ESCC). Methods: A total of 249 patients who received radical esophagectomy at Fudan University Shanghai Cancer Center were divided into training set and testing set. 89 patients with ESCC from TCGA database were enrolled into validation set. Myeloid cells in tumor microenvironment were evaluated by immunohistochemistry or CIBERSORT, and then were included into LASSO cox regression model to construct immunoscore. The predictive value of immunoscore for prognosis after surgery or ACT was analyzed. Results: Immunoscore was constructed by 4 types of myeloid cells including macrophages, neutrophils, mast cells and dendritic cells, and was demonstrated as IS=2^(0.527719*Mφ -0.2604269*MC-0.4812935*DC-0.4519706*Neu). The overall survival was significantly different between 2 immunotypes, which were divided according to the immunoscore, in all sets (P<0.001, P=0.005, and P=0.002, respectively). And immunotype A was identified as an independent predictor for survival benefit in all 3 sets (HR=2.068, P=0.005; HR=2.028, P=0.007; HR=6.474, P=0.007; respectively). In patients who received ACT, immunotype A was significantly related to longer overall survival in both training set (P<0.001) and testing set (P=0.011). The nomogram based on immunotype and other clinicopathological factors showed good efficiency of predicting response to ACT. Finally, several important cytokines and pathways were highly enriched in immunoscore A subgroup. Conclusion: The immunoscore was an effective prognostic predictor in ESCC for patients undergoing surgical resection and receiving ACT.

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“…In study demonstrated here, we employed gene transfection to establish PHM1-41 cervical stromal cells overexpressing CXCL1, which can secrete a respectably high level of CXCL1 into medium, and the supernatants derived from medium of CXCL1 overexpressing PHM1-41cell can behave as a promoting mediator for the growth and migration of HeLa cells, indicating that a CXCL1 paracrine manner plays a crucial role in tumor-associated malignant behaviors. Coupled with this, our laboratory also previously revealed the critical CXCL3-paracrine mechanism, by which supernatants derived from stromal cells overexpressing CXCL3 raised the abilities of HeLa cell growth and migration [33].…”

Section: Discussionmentioning

confidence: 72%

High-level expression of CXCL1/GROα in uterine cervix cancer is linked to advanced stage and facilitates tumor cell malignant processes in an autocrine/paracrine manner

Man¹,

Yang²,

Wei³

et al. 2020

Preprint

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Background It has previously accepted that several types of human cancer constitutively express CXCL1, which may implicated in various aspects of tumors. Here, we sought to assess the expression and of CXCL1 in human uterine cervix cancer (UCC) and its potential role and mechanism in UCC. Methods CXCL1 protein expression in a uterine cervical tissue microarray was assessed by immunohistochemistry. The roles of CXCL1 on HeLa UCC cells were detected by CCK-8, transwell and apoptosis assays. Western blotting and ERK1/2 blocker PD98059 were utilized to explore whether ERK signal was implicated in CXCL1-mediated UCC processes. Results CXCL1 was expressed by HeLa, PHM1-41 cells as well as cervical tissues, in which UCC tissues showed an obviously high level of CXCL1 compared with non-cancerous tissues. Additionally, of the cancer tissues, CXCL1 high-level expression was notably relevant to poor clinical stages. In vitro, the growth and migration of HeLa cells were enhanced in the presence of exogenous CXCL1. Gain-function assays revealed that CXCL1 overexpression promoted growth and migration response to HeLa cells via autocrine/paracrine manners. Moreover, CXCL1 also led to the inhibition of apoptosis in HeLa cells. Finally, CXCL1 overexpression in HeLa cells influenced the expression of ERK signal-related genes including ERK, p-ERK, cyclin D1 and Bax, and cell malignant behaviors derived from CXCL1 overexpresion were further interrupt in the presence of PD98059. Conclusion Our findings provided the potential roles of CXCL1 as a promoter and the novel understanding of the functional relation of CXCL1 with ERK signal pathway in UCC.

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CXCL3 overexpression promotes the tumorigenic potential of uterine cervical cancer cells via the MAPK/ERK pathway

Cited by 36 publications

References 36 publications

Differences in gynecologic tumor development in Amhr2-Cre mice with KRASG12D or KRASG12V mutations

Differences in gynecologic tumor development in Amhr2-Cre mice with KRASG12D or KRASG12V mutations

WITHDRAWN: Immunoscore Signature Predicts Postoperative Survival and Adjuvant Chemotherapeutic Benefits in Esophageal Squamous Cell Carcinoma

High-level expression of CXCL1/GROα in uterine cervix cancer is linked to advanced stage and facilitates tumor cell malignant processes in an autocrine/paracrine manner

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