CD36 upregulates DEK transcription and promotes cell migration and invasion via GSK-3β/β-catenin-mediated epithelial-to-mesenchymal transition in gastric cancer

Wang, Jin; Wen, Ti; Li, Zhi; Che, Xiaofang; Gong, Libao; Jiao, Zihan; Qu, Xiujuan; Liu, Yunpeng

doi:10.18632/aging.103985

Cited by 32 publications

(25 citation statements)

References 30 publications

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“…In addition, the expression of CD36 was significantly associated with current predictors for the efficacy of ICIs. The practical application value of CD36 is disease specific [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Prognostic and immunological role of CD36: A pan-cancer analysis

Chen¹,

Liao²,

Huang³

et al. 2021

J. Cancer

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CD36 plays a critical role in lipid metabolism, which is closely associated with human immunity. However, the role of CD36 in cancer remains unclear. We performed a pan-cancer analysis to elucidate the potential role of CD36 in cancer by investigating its prognostic value and current predictors for the efficacy of immune checkpoint inhibitors (ICIs) in multiple cancer types. CD36 expression in cancer cell lines, tumor tissue, and their adjacent normal tissues displayed heterogeneity among different cancers. Immunohistochemistry was used to detect CD36 expression and confirmed the results. CD36 expression significantly affects prognosis in the six cancer types. High CD36 expression was marginally associated with poorer prognosis in four of them and improved prognosis in the remaining two types. CD36 expression was significantly correlated with the 6 immune infiltrates in most cancer types. In addition, CD36 gene expression was positively correlated with Stromal score, Immune score, and ESTIMATE score. A total of 47 immune checkpoint genes were collected and their relationship with CD36 expression was analyzed. CD36 expression was significantly associated with multiple stimulatory and inhibitory checkpoint molecules with a disease-specific pattern. As to the genes reported to positively relate to the efficacy of ICIs, CD36 expression was positively correlated with most of them but negatively associated with a small proportion of cancer type-specific patterns. Concerning the genes negatively related to the efficacy of ICIs, CD36 expression was positively correlated with NRP1 and TNFSF15 in multiple cancers. CD36 expression was negatively correlated with tumor neoantigen burden in most cancer types. However, CD36 expression was negatively correlated with tumor mutation burden in most cancer types. The correlation between CD36 expression and the four methyltransferases was also significant in multiple cancers, but also with a cancer type-specific pattern. In summary, the current study found CD36 expression and its prognostic value in multiple cancer types. In addition, the expression of CD36 was significantly associated with current predictors for the efficacy of ICIs. The practical application value of CD36 is disease specific.

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Section: Discussionmentioning

confidence: 99%

Prognostic and immunological role of CD36: A pan-cancer analysis

Chen¹,

Liao²,

Huang³

et al. 2021

J. Cancer

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“…CD36, a fatty acid translocase, is critical for the regulation of lipid metabolism in GC cells 22,23,68 . Overexpression of CD36 results in elevated fatty acid uptake and could be a confirmatory marker for EMT to a more aggressive phenotype in various tumors, 69–71 including GC 21 . Although APOC2 has been reported to interact with CD36 and initiate downstream signaling in diseases, 11,24 the collaboration between APOC2 and CD36 needs to be further confirmed in GC.…”

Section: Discussionmentioning

confidence: 99%

“… 22 , 23 , 68 Overexpression of CD36 results in elevated fatty acid uptake and could be a confirmatory marker for EMT to a more aggressive phenotype in various tumors, 69 , 70 , 71 including GC. 21 Although APOC2 has been reported to interact with CD36 and initiate downstream signaling in diseases, 11 , 24 the collaboration between APOC2 and CD36 needs to be further confirmed in GC. Our data demonstrated that both CD36 and APOC2 were indispensable for GC migration, invasion, and proliferation.…”

Section: Discussionmentioning

confidence: 99%

“… 20 In GC cells, fatty acids can upregulate CD36 expression to trigger the epithelial to mesenchymal transition (EMT) process, thereby promoting tumor growth and omental metastasis. 21 , 22 , 23 It has been previously reported that APOC2 interacts with CD36 to trigger downstream signaling in acute myeloid leukemia (AML) and atherosclerosis. 11 , 24 However, it is unclear whether APOC2 interacts with CD36 to regulate EMT in GC.…”

Section: Introductionmentioning

confidence: 99%

“…CD36 is a multiligand class B scavenger receptor that functions in lipid metabolism and is involved in various cellular processes 20 . In GC cells, fatty acids can upregulate CD36 expression to trigger the epithelial to mesenchymal transition (EMT) process, thereby promoting tumor growth and omental metastasis 21–23 . It has been previously reported that APOC2 interacts with CD36 to trigger downstream signaling in acute myeloid leukemia (AML) and atherosclerosis 11,24 .…”

Section: Introductionmentioning

confidence: 99%

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Apolipoprotein C‐II induces EMT to promote gastric cancer peritoneal metastasis via PI3K/AKT/mTOR pathway

Wang

Yang

et al. 2021

Clinical & Translational Med

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Background Peritoneal metastasis (PM) occurs frequently in patients with gastric cancer (GC) and confers poor survival. Lipid metabolism acts as a non‐negligible regulator in epithelial–mesenchymal transition (EMT), which is crucial for the metastasis of GC. As apolipoprotein C2 (APOC2) is a key activator of lipoprotein lipase for triglyceride metabolism, the exact mechanism of APOC2 remains largely unknown in GC. Methods Tandem mass tags identified differentially expressed proteins between human PM and GC tissues, and showed that APOC2 overexpressed in PM tissues, which was further confirmed by immunoblotting, immunohistochemistry, and ELISA. Global gene expression changes were identified in APOC2 knockdown cells via RNA‐sequencing. The role of APOC2 in lipid metabolism of GC cells was assessed via the Seahorse XF analyzer and lipid staining assays. The biological role of APOC2 in GC cells was determined by 3D Spheroid invasion, apoptosis, colony formation, wound healing, transwell assay, and mouse models. The interaction between APOC2 and CD36 was analyzed by co‐immunoprecipitation and biolayer interferometry. The underlying mechanisms were investigated using western blot technique. Results APOC2 overexpressed in GC PM tissues. Upregulation of APOC2 correlated with a poor prognosis in GC patients. APOC2 promoted GC cell invasion, migration, and proliferation via CD36‐mediated PI3K/AKT/mTOR signaling activation. Furthermore, APOC2‐CD36 axis upregulated EMT markers of GC cells via increasing the phosphorylation of PI3K, AKT, and mTOR. Knockdown either APOC2 or CD36 inhibited the malignant phenotype of cancer cells, and delayed GC PM progression in murine GC models. Conclusion APOC2 cooperates with CD36 to induce EMT to promote GC PM via PI3K/AKT/mTOR pathway. APOC2‐CD36 axis may be a potential target for the treatment of aggressive GC.

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CD36: an emerging therapeutic target for cancer and its molecular mechanisms

Ruan

Meng

2022

J Cancer Res Clin Oncol

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CD36 upregulates DEK transcription and promotes cell migration and invasion via GSK-3β/β-catenin-mediated epithelial-to-mesenchymal transition in gastric cancer

Cited by 32 publications

References 30 publications

Prognostic and immunological role of CD36: A pan-cancer analysis

Prognostic and immunological role of CD36: A pan-cancer analysis

Apolipoprotein C‐II induces EMT to promote gastric cancer peritoneal metastasis via PI3K/AKT/mTOR pathway

CD36: an emerging therapeutic target for cancer and its molecular mechanisms

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