Lipophagy-ICAM-1 pathway associated with fatty acid and oxygen deficiencies is involved in poor prognoses of ovarian clear cell carcinoma

Koizume, Shiro; Takahashi, Tomoko; Nakamura, Yoshiyasu; Yoshihara, Masaharu; Ota, Yoshihide; Sato, Shinya; Tadokoro, Hiroko; Yokose, Tomoyuki; Kato, Hiroyuki; Miyagi, Etsuko; Miyagi, Yohei

doi:10.1038/s41416-022-01808-4

Cited by 5 publications

(25 citation statements)

References 49 publications

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“…Data shown are the mean ( n = 2) ± SD. (H) Effect of chloroquine (CQ) on CD69 expression in OVSAYO cells under SSH for 48 h. Increased LC3A/B‐II level is a marker of lipophagy inhibition 10 . (I) Histograms of flow cytometry (FCM) analysis of cell surface CD69 in OVSAYO cells cultured under the indicated conditions for 39 h. (J) Histograms of FCM analysis of CD69 expressed in Jurkat cells cultured with and without PMA (10 ng/mL) for 18 h. HIF‐2α, hypoxia‐inducible factor‐2α; HP‐Alb, high‐purity albumin; LCFA, long‐chain fatty acid; LP‐Alb, low‐purity albumin; Ole, oleic acid; Pal, palmitic acid; SSN, serum starvation and normoxia; V, vehicle…”

Section: Resultsmentioning

confidence: 99%

“…For immunocytochemistry of ECAD and VIM, cells (5 × 10 4 ) were seeded into 4‐well chamber polystyrene vessels (#354114; Corning) and then cultured under the indicated conditions. Following experiments were carried out as previously described 10 …”

Section: Methodsmentioning

confidence: 99%

“…Routinely processed formalin‐fixed, paraffin‐embedded specimens were prepared from 130 EOC patients for a TMA (Table S1) and for 77 whole‐slide sections of CCC (Table S2) at Kanagawa Cancer Center Hospital 10 . Immunohistochemistry was undertaken 9 using anti‐CD69 (#373798; Santa Cruz Biotechnology) and anti‐FN (A0245; Dako) Abs.…”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry was undertaken 9 using anti‐CD69 (#373798; Santa Cruz Biotechnology) and anti‐FN (A0245; Dako) Abs. Immunoreactivity was visualized as previously described 10 …”

Section: Methodsmentioning

confidence: 99%

“…9,10 We revealed that LCFAs and O 2 deficiencies followed by lipophagy-driven degradation of lipid droplets causes stabilization of NF-κB binding to induce synergistic ICAM1 expression. 10 ICAM-1 contributes to cell survival under SSH and tumor growth. 9 We showed that multiple genes such as KLF6, 9 JUN, 9 and FVII 11 are also synergistically activated in CCC cells with O 2 depletion in response to LCFA (KLF6 and JUN) 9 and cholesterol (FVII) 11 insufficiency.…”

Section: Introductionmentioning

confidence: 98%

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Cancer cell‐derived CD69 induced under lipid and oxygen starvation promotes ovarian cancer progression through fibronectin

et al. 2023

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Cancer tissues generally have molecular oxygen and serum component deficiencies because of poor vascularization. Recently, we revealed that ICAM1 is strongly activated through lipophagy in ovarian clear cell carcinoma (CCC) cells in response to starvation of long-chain fatty acids and oxygen and confers resistance to apoptosis caused by these harsh conditions. CD69 is a glycoprotein that is synthesized in immune cells and is associated with their activation through cellular signaling pathways.However, the expression and function of CD69 in nonhematological cells is unclear.Here, we report that CD69 is induced in CCC cells as in ICAM1. Mass spectrometry analysis of phosphorylated peptides followed by pathway analysis revealed that CD69 augments CCC cell binding to fibronectin (FN) in association with the phosphorylation of multiple cellular signaling molecules including the focal adhesion pathway. Furthermore, CD69 synthesized in CCC cells could facilitate cell survival because the CD69-FN axis can induce epithelial-mesenchymal transition. Experiments with surgically removed tumor samples revealed that CD69 is predominantly expressed in CCC tumor cells compared with other histological subtypes of epithelial ovarian cancer.Overall, our data suggest that cancer cell-derived CD69 can contribute to CCC progression through FN.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry was undertaken 9 using anti‐CD69 (#373798; Santa Cruz Biotechnology) and anti‐FN (A0245; Dako) Abs. Immunoreactivity was visualized as previously described 10 …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Cancer cell‐derived CD69 induced under lipid and oxygen starvation promotes ovarian cancer progression through fibronectin

et al. 2023

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Sam68 is a druggable vulnerability point in cancer stem cells

da Silva,

Yevdokimova,

Benoit

2023

Cancer Metastasis Rev

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Sam68 (Src associated in mitosis of 68 kDa) is an RNA-binding and multifunctional protein extensively characterized in numerous cellular functions, such as RNA processing, cell cycle regulation, kinase- and growth factor signaling. Recent investigations highlighted Sam68 as a primary target of a class of reverse-turn peptidomimetic drugs, initially developed as inhibitors of Wnt/β-catenin mediated transcription. Further investigations on such compounds revealed their capacity to selectively eliminate cancer stem cell (CSC) activity upon engaging Sam68. This work highlighted previously unappreciated roles for Sam68 in the maintenance of neoplastic self-renewal and tumor-initiating functions. Here, we discuss the implication of Sam68 in tumorigenesis, where central findings support its contribution to chromatin regulation processes essential to CSCs. We also review advances in CSC-targeting drug discovery aiming to modulate Sam68 cellular distribution and protein-protein interactions. Ultimately, Sam68 constitutes a vulnerability point of CSCs and an attractive therapeutic target to impede neoplastic stemness in human tumors.

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Bibliometric analysis of lipophagy:2013 to 2023

Zhao,

Pang,

et al. 2024

Heliyon

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Lipophagy-ICAM-1 pathway associated with fatty acid and oxygen deficiencies is involved in poor prognoses of ovarian clear cell carcinoma

Cited by 5 publications

References 49 publications

Cancer cell‐derived CD69 induced under lipid and oxygen starvation promotes ovarian cancer progression through fibronectin

Cancer cell‐derived CD69 induced under lipid and oxygen starvation promotes ovarian cancer progression through fibronectin

Sam68 is a druggable vulnerability point in cancer stem cells

Bibliometric analysis of lipophagy:2013 to 2023

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