LPCAT1 Promotes Cutaneous Squamous Cell Carcinoma via EGFR-Mediated Protein Kinase B/p38MAPK Signaling Pathways

Huang, Yingjian; Wang, Yuqian; Wang, Yan; Wang, Ning; Duan, Qiangde; Wang, Shengbang; Li, Meng; Bilal, Muhammad; Zheng, Yan

doi:10.1016/j.jid.2021.07.163

Cited by 18 publications

(21 citation statements)

References 49 publications

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“…According to the foregoing literature, the LPCAT1-EGFR positive feedback loop contributes to the tumorigenesis of glioma cells [19]. In cutaneous squamous cell carcinoma, LPCAT1 promotes progression via the EGFR-mediated AKT/p38MAPK signaling pathways [26]. Coincidentally, EGFR/ PI3K/AKT signaling has been closely associated with the occurrence of drug resistance and the transformation from LUAD to lung squamous carcinoma among NSCLC cells [5,27,28].…”

Section: Discussionmentioning

confidence: 99%

LPCAT1 promotes gefitinib resistance via upregulation of the EGFR/PI3K/AKT signaling pathway in lung adenocarcinoma

Ding¹,

Ding²,

Leng³

2022

J. Cancer

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Currently, the mechanisms of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance have been a focus of clinical research. Despite that most of the mechanisms of acquired EGFR TKI resistance have been revealed, about 30% of non-small-cell lung cancer (NSCLC) cases have not been fully elucidated, especially for lung adenocarcinoma (LUAD). Recently, LPCAT1, an important enzyme of phospholipid metabolism, has been found to bridge the gap between the oncogene and metabolic reprogramming. In NSCLC, LPCAT1 has been shown to participate in progression and metastasis. However, little is known about the role of LPCAT1 in acquired EGFR TKI resistance. In this study, elevated LPCAT1 expressions were observed in an EGFR TKI-resistant cell line (PC-9R) relative to a corresponding EGFR TKI-sensitive cell line (PC-9). In vivo and in vitro gene functional studies showed that LPCAT1 contributed to the pathogenesis of gefitinib resistance in LUAD, where an LPCAT1-EGFR positive feedback loop formed and then regulated its downstream signaling molecules of the EGFR/PI3K/AKT signaling pathway. The results provided novel insights into the acquired resistance mechanism of EGFR TKI from the perspective of phospholipid metabolism. These findings suggest LPCAT1 may serve as a potential therapeutic target for patients with EGFR TKI-resistant NSCLC.

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Section: Discussionmentioning

confidence: 99%

LPCAT1 promotes gefitinib resistance via upregulation of the EGFR/PI3K/AKT signaling pathway in lung adenocarcinoma

Ding¹,

Ding²,

Leng³

2022

J. Cancer

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“…Wei demonstrated that LPCAT1 was up-regulated in NSCLC cells and tissues, and promoted NSCLC progression via PI3K/AKT/MYC pathway, can be used as a target for the NSCLC treatment [ 23 ]. LPCAT1 was found to contribute to cutaneous squamous cell carcinoma progression through EGFR-mediated protein kinase B and p38MAPK signaling pathways [ 24 ]. High-LPCAT1 expression could inhibit STAT1 expression, up-regulate CyclinD1, CyclinE, CDK4 and MMP-9, and decrease p27kip1 to promote cancer progression in HCC [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma

Wang

Ding

et al. 2022

Eur J Med Res

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Background Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is overexpressed in multiple human tumors. However, the role of LPCAT1 in hepatocellular carcinoma (HCC) has not been understood. We aim to explore the relationships between LPCAT1 expression and prognosis, clinicopathological features, tumor microenvironment (TME), immune cell infiltration, immune checkpoint gene expression, and related signaling pathways in HCC. Furthermore, we also explored the relationship between LPCAT1 expression and drug sensitivity to HCC treatment. Methods The expression profiles were acquired from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (THPA). Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm. Results LPCAT1 was overexpressed in HCC, and its expression was related to poor prognosis, LPCAT1 was an independent prognostic biomarker in HCC. Expression of LPCAT1 increased statistically with the increase of clinical stage and grade of HCC patients. GO and KEGG network analysis revealed that LPCAT1 positively associated molecules were mostly enriched in functions related to cell adhesion. The TME score of high-LPCAT1 group was significantly higher than that of low-LPCAT1 group. Immune infiltrating cells positively correlated with LPCAT1 expression were Macrophages M0, B cells memory, Dendritic cells activated, T cells regulatory and T cells gamma delta in HCC. We found a positive correlation between LPCAT1 and most immune checkpoint gene expression. The IC50 of 5-Fluorouracil, Gemcitabine, Mitomycin C, Sorafenib and Cabozantinib in patients with high-LPCAT1 expression was lower than that in patients with low-LPCAT1 expression. Our findings provide a wealth of information for further understanding of the biological functions and signaling pathways of LPCAT1 in HCC. Conclusions LPCAT1 is an independent prognostic biomarker and associated with tumor microenvironment, immune cell infiltration, immune checkpoint expression and drug sensitivity in hepatocellular carcinoma.

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“…Recently, LPCAT1 has been reported to contribute to cancer initiation and progression in various cancer types. Upregulation of LPCAT1 was found in numerous solid cancers and was correlated with multiple tumor malignant characteristics including progression, metastasis, recurrence and poor prognosis by promoting epithelial-mesenchymal transition, tumor microenvironment, tumor immune infiltration and chemoresistance [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Mechanistically, LPCAT1 inhibited tumor suppressor gene STAT1 expression, up-regulated Cyclins to promote HCC progression [14].…”

Section: Discussionmentioning

confidence: 99%

“…Among these members, LPCAT1 has attracted much attention in a variety of cancers. So far, LPCAT1 has been found to be overexpressed in various solid cancers including prostate cancer [11], hepatocellular carcinoma [12][13][14][15][16], breast cancer [17,18], endometrial cancer [19], oral squamous cell carcinoma [20], esophageal squamous cell carcinoma [21], cutaneous squamous cell carcinoma [22], lung adenocarcinoma [23,24] and its overexpression promoted the progression, metastasis, recurrence and worsened survival of these solid cancers. However, the pattern of LPCAT1 expression and its clinical relevance have been rarely studied in AML.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of down-regulated LPCAT1 expression in acute myeloid leukemia

Chen

Lin

et al. 2022

Preprint

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Background Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression has been found in various solid cancers and promoted the progression, metastasis, and recurrence of these diseases. However, the expression pattern of LPCAT1 in acute myeloid leukemia was unclear. This study aimed to assess expression status of LPCAT1 and its clinical relevance in acute myeloid leukemia (AML). Methods and Results LPCAT1 expression was significant lower in AML than controls predicted by public databases. Also, a significantly down-regulated of LPCAT1 of bone marrow in AML compared with controls was validated by real-time quantitative PCR (RQ-PCR) [0.056 (0.000-0.846) vs 0.253 (0.031-1.000)]. The DiseaseMeth version 2.0 and The Cancer Genome Atlas analysis showed LPCAT1 promoter was hypermethylated in AML and a strongly negative correlation was found between LPCAT1 expression and methylation (R=-0.610, P<0.001). RQ-PCR revealed the frequency of LPCAT1 low-expression in FAB-M4/M5 subtype was lower than other subtypes (P=0.018). The ROC curve revealed LPCAT1 expression might serve as a potential diagnostic marker for differentiating AML from normal with an area under the ROC curve of 0.819 (95% CI 0.743-0.894, P<0.001). In cytogenetically normal AML, the overall survival in patients with LPCAT1 low-expression was significantly longer than that in those without LPCAT1 low-expressed group (median 19 versus 5.5 months, P=0.036). Conclusion LPCAT1 is downregulated in bone marrow and LPCAT1 expression can be as a potential biomarker for diagnosis and evaluating prognosis in AML.

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LPCAT1 Promotes Cutaneous Squamous Cell Carcinoma via EGFR-Mediated Protein Kinase B/p38MAPK Signaling Pathways

Cited by 18 publications

References 49 publications

LPCAT1 promotes gefitinib resistance via upregulation of the EGFR/PI3K/AKT signaling pathway in lung adenocarcinoma

LPCAT1 promotes gefitinib resistance via upregulation of the EGFR/PI3K/AKT signaling pathway in lung adenocarcinoma

LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma

Clinical significance of down-regulated LPCAT1 expression in acute myeloid leukemia

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