Overexpression of PD‐L1 causes germ cells to slough from mouse seminiferous tubules via the PD‐L1/PD‐L1 interaction

Fang, Lian; Feng, Rui; Liang, Weiye; Liu, Fang‐Fang; Bian, Ganlan; Yu, Caiyong; Guo, Hongbo; Cao, Yihui; Liu, Mingkai; Zuo, Jia; Peng, Yinglong; Zhao, Jie; Sun, Ruixia; Shan, Jiajie; Wang, Jian

doi:10.1111/jcmm.17305

Cited by 4 publications

(9 citation statements)

References 53 publications

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“…In this study, combined with previous studies that found that PD-L1 can bind to PD-L1 to cause cell detachment, 7…”

Section: Discussionsupporting

confidence: 58%

“…We transfected SW480 cells with PD‐L1‐HA expression lentivirus, and the mRNA and protein levels of PD‐L1 substantially increased in PD‐L1 expression lentivirus‐transfected SW480 cells (Figure 2C,D), and PD‐L1 was mainly localized to the cell membrane by immunocytochemistry assay (Figure 2F). We found that PD‐L1 with HA in CRC cells could bind to PD‐L1 with FLAG (Figure 2E), and in a previous study we found that PD‐L1 interacted with PD‐L1 to cause cell shedding 7 . Then, we investigated the effect of PD‐L1/PD‐L1 on the migration of CRC cells.…”

Section: Resultsmentioning

confidence: 71%

“…26,27 In a previous study, we found that overexpression of PD-L1 causes germ cell shedding and that PD-L1 can bind to PD-L1 in colorectal cancer (CRC) cells. 7 In this study, we found that PD-L1/PD-L1 mediates the adhesion, migration and proliferation functions of CRC cells. Therefore, Colorectal cancer is the third most common tumour in the world, and nearly 2 million patients were diagnosed with CRC in 2020.…”

Section: Discussionmentioning

confidence: 66%

“…The roles of PD‐1/PD‐L1 in cancer development and metastasis have attracted increasing attention 26,27 . In a previous study, we found that overexpression of PD‐L1 causes germ cell shedding and that PD‐L1 can bind to PD‐L1 in colorectal cancer (CRC) cells 7 . In this study, we found that PD‐L1/PD‐L1 mediates the adhesion, migration and proliferation functions of CRC cells.…”

Section: Discussionmentioning

confidence: 74%

“…5,6 To further investigate the molecular function and mechanism of PD-L1, we constructed PD-L1 transgenic mice and found that simultaneous expression of PD-L1 on germ cells and Sertoli cells will cause PD-L1 to bind and interact with PD-L1 and thus cause germ cell detachment. 7 Due to the special physiological structure of the seminiferous tubule, germ cells only contact adjacent Sertoli cells, which provide structural and nutritional support. 8 In addition, the significance of ERK signalling, which can be activated by the nonclassical actions of testosterone, is necessary for maintaining ectoplasmic specialization (ES) connections.…”

mentioning

confidence: 99%

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PD‐L1/PD‐L1 signalling promotes colorectal cancer cell migration ability through RAS/MEK/ERK

Cao

Fang

Liang

et al. 2022

Clin Exp Pharma Physio

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Programmed death ligand 1 (PD-L1) is widely known as an immune checkpoint, and immunotherapy through the inhibition of checkpoint molecules has become an important component in the successful treatment of tumours via programmed death 1 (PD-1)/PD-L1 signalling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) are elusive. We previously found that PD-L1 can bind to PD-L1 and cause cell detachment. However, the detailed molecular mechanisms of how PD-L1 binds to PD-L1 and how it transmits signals to the cell remain unclear. In this study, we disclosed that PD-L1 expression was dramatically upregulated in CRC compared to normal tissues. Ectopic expression of PD-L1 inhibits cell adhesive capacity and promotes cell migration in CRC cell lines, while silencing PD-L1 had the opposite effects and suppressed invasion and proliferation. Mechanistically, PD-L1 was found to promote epithelial-mesenchymal transition (EMT) through the ERK signalling molecule pathway and interacted with the 1-86 aa fragment of KRAS to transduce signals. Collectively, our study demonstrated the role of PD-L1 after binding to PD-L1 in CRC, thereby providing a new theoretical basis for further improving immunotherapy with anti-PD-L1 antibodies.

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“…In this study, combined with previous studies that found that PD-L1 can bind to PD-L1 to cause cell detachment, 7…”

Section: Discussionsupporting

confidence: 58%

Section: Resultsmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

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PD‐L1/PD‐L1 signalling promotes colorectal cancer cell migration ability through RAS/MEK/ERK

Cao

Fang

Liang

et al. 2022

Clin Exp Pharma Physio

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Overexpression of PD-L1 causes germ cell failure and infertility via CRISP1/PD-L1 interaction in mouse epididymis

Li,

Guo

2024

Zygote

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Summary Spermatogenesis is a highly complex process through which mature sperms are produced, and it requires three important stages; mitosis, meiosis and sperm formation. The expression of genes regulated by transcription factors at specific stages exerts important regulatory effects on the development process of germ cells. Male mice with overexpressed programmed death ligand 1 (PD-L1) (B7 homolog1) in the testis have infertility and abnormal sperm development, thereby exhibiting severe malformation and sloughing throughout spermatid maturation and collapsed and disorganized seminiferous epithelium structure. Furthermore, PD-L1 overexpression causes overexpression of cysteine-rich secretory protein 1 (CRISP1) in the epididymis and adversely affects or precludes sperm energization, sperm-pellucida binding and sperm-oocyte fusion. These findings suggest that CRISP1 and PD-L1 can interact with each other to induce male infertility and germ-cell dissociation.

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