Cancer Cell-derived CD69 Induced Under Lipid and Oxygen Starvation Promotes Ovarian Cancer Progression Through Fibronectin

Overview

Journal Cancer Sci

Specialty Oncology

Date 2023 Feb 28

PMID 36854451

Authors

Shiro Koizume

Tomohiko Kanayama

Yayoi Kimura

Hisashi Hirano

Tomoko Takahashi

Yukihide Ota

Kaoru Miyazaki

Mitsuyo Yoshihara

Yoshiyasu Nakamura

Tomoyuki Yokose

Hisamori Kato

Katsuya Takenaka

Shinya Sato

Hiroko Tadokoro

Etsuko Miyagi

Yohei Miyagi

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Koizume S, Takahashi T, Miyagi Y Front Pharmacol. 2024; 15:1437161.

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