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

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.

CD69 is a Promising Immunotherapy and Prognosis Prediction Target in Cancer

“…The CD69 expressed in cancer cells facilitated the progression of carcinoma cell through its interaction with fibronectin, consequently contributing to an adverse prognosis for patients. 69 Another study found a subset of leukemia stem cells with high CD69 expression levels corresponding to self-renewal and enhanced colony-forming capacity, which is responsible for the relapse of acute myeloid leukemia 70 , 71 and poor and poor clinical outcomes. 70 Moreover, CD69 expression was also detected on tumor cells from most other hematological malignancies and was associated with poor clinical outcome.…”

“… [ 72 ] CLL CD5 + CD19 + CLL cells CD69 + plus ZAP-70 + or CD38 + or immunoglobulin variable heavy chain gene unmutated patients had the worst PFS and OS [ 73 ] OCCC Ovarian clear cell carcinoma cells The CD69 expressed in cancer cells has been found to facilitate the progression of OCCC through its interaction with fibronectin, consequently contributing to an adverse prognosis for patients. [ 69 ] Abbreviations : HNSCC, head and neck squamous cell carcinoma; OS, overall survival; OCCC, Ovarian clear cell carcinoma; CRC, colorectal cancer; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung carcinoma; TIL, tumor-infiltrating lymphocyte; UBC, urinary bladder cancer; MM, multiple myeloma; AML, acute myeloid leukemia; HSC, hematopoietic stem cell; CLL, chronic lymphocytic leukemia; B-NHL, B-cell non-Hodgkin’s lymphoma; PFS, progression free survival. …”

Lipid droplets: a candidate new research field for epithelial ovarian cancer

“…This LD catabolism synergistically activates multiple genes, including ICAM1 and CD69 , through activation of transcription factor NFκB binding to their promoter regions ( Koizume et al, 2022 ). The proteins encoded by these genes lead to malignant phenotypes, such as apoptosis resistance ( Koizume et al, 2015 ) and epithelial-to-mesenchymal transition with assistance of extracellular fibronectin ( Koizume et al, 2023 ). Thus, we hypothesized that LDs may play major roles in OCCC progression, similar to the case for ccRCC.…”