PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression

Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potent...

Full description

Saved in:

Bibliographic Details
Published in:	International journal of molecular sciences Vol. 24; no. 7; p. 6420
Main Authors:	Alkaabi, Duaa, Arafat, Kholoud, Sulaiman, Shahrazad, Al-Azawi, Aya Mudhafar, Attoub, Samir
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 29-03-2023 MDPI
Subjects:	AKT protein Animals Apoptosis B7-H1 Antigen - metabolism Binding Breast cancer c-Fos protein c-Myc protein CAM Cell adhesion & migration Cell growth Cell Line, Tumor Cell proliferation Chick Embryo Chorioallantoic membrane Cloning CRISPR Development and progression Embryos Gastric cancer Health aspects Humans invasion Lymphocytes Lymphocytes T Malignancy Medical prognosis Melanoma Metastases Metastasis migration Mortality Myc protein Neoplasm Recurrence, Local PD-1 protein PD-L1 PD-L1 protein Prognosis Programmed Cell Death 1 Receptor - genetics proliferation Protein binding Proteins RhoA protein Survivin T cells TNBC Triple Negative Breast Neoplasms - metabolism Tumors United Kingdom invasion proliferation PD-L1 migration Akt TNBC CAM ERK
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potential targets. Programmed death-ligand 1 (PD-L1) is an immunosuppressive protein that inactivates T cells by binding to the inhibitory receptor programmed death-1 (PD-1). PD-L1 overexpression in cancer cells contributes to immune evasion and, subsequently, poor survival and prognosis in several cancers, including breast cancer. Apart from its inhibitory impact on T cells, this ligand is believed to have an intrinsic role in cancer cells. This study was performed to clarify the PD-1 independent role of PD-L1 in TNBC MDA-MB-231 cells by knocking out the PD-L1 using three designs of CRISPR-Cas9 lentiviral particles. Our study revealed that PD-L1 knockout significantly inhibited MDA-MB-231 cell proliferation and colony formation in vitro and tumor growth in the chick embryo chorioallantoic membrane (CAM) model in vivo. PD-L1 knockout also decreased the migration and invasion of MDA-MB-231 cells in vitro. We have shown that PD-L1 knockout MDA-MB-231 cells have low levels of p-Akt and p-ERK in addition to some of their downstream proteins, c-Fos, c-Myc, p21, survivin, and COX-2. Furthermore, PD-L1 knockout significantly decreased the expression of Snail and RhoA. This study shows the intrinsic role of PD-L1 in TNBC independently of its binding to PD-1 receptors on T cells. It may pave the way for developing novel therapeutic strategies using PD-L1 inhibitors alone and in combination to treat TNBC more effectively.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms24076420