Topic
Cancer cell
About: Cancer cell is a research topic. Over the lifetime, 93402 publications have been published within this topic receiving 3512390 citations. The topic is also known as: cancerous cell & tumor cell.
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TL;DR: Insight is provided into the biology of PD-L1 regulation, a previously unrecognized master regulator of this critical immune checkpoint is identified, and a potential therapeutic target to overcome immune evasion by tumour cells is highlighted.
Abstract: Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression. CMTM6 is not required for PD-L1 maturation but co-localizes with PD-L1 at the plasma membrane and in recycling endosomes, where it prevents PD-L1 from being targeted for lysosome-mediated degradation. Using a quantitative approach to profile the entire plasma membrane proteome, we find that CMTM6 displays specificity for PD-L1. Notably, CMTM6 depletion decreases PD-L1 without compromising cell surface expression of MHC class I. CMTM6 depletion, via the reduction of PD-L1, significantly alleviates the suppression of tumour-specific T cell activity in vitro and in vivo. These findings provide insights into the biology of PD-L1 regulation, identify a previously unrecognized master regulator of this critical immune checkpoint and highlight a potential therapeutic target to overcome immune evasion by tumour cells.
561 citations
TL;DR: The recent progress of the regulation of PD-L1 expression in cancer cells is summarized, a regulatory model for unified explanation is proposed and Clinically, it could increase treatment efficacy of targeted therapy by choosing those molecules that control both PD- L1 expression and cell proliferation.
560 citations
TL;DR: Two functional screens for proteins required for the invasion of fibrosarcoma cells that identified the molecular chaperone heat shock protein 90 are described, indicating that cell-impermeant anti-hsp90 drugs might decrease invasiveness without the concerns inherent in inhibiting intracellular hsp90.
Abstract: Tumour cell invasiveness is crucial for cancer metastasis and is not yet understood. Here we describe two functional screens for proteins required for the invasion of fibrosarcoma cells that identified the molecular chaperone heat shock protein 90 (hsp90). The hsp90 alpha isoform, but not hsp90 beta, is expressed extracellularly where it interacts with the matrix metalloproteinase 2 (MMP2). Inhibition of extracellular hsp90 alpha decreases both MMP2 activity and invasiveness. This role for extracellular hsp90 alpha in MMP2 activation indicates that cell-impermeant anti-hsp90 drugs might decrease invasiveness without the concerns inherent in inhibiting intracellular hsp90.
560 citations
TL;DR: The transcription factor MYB has been identified as an oncogene that is involved in some human leukaemias and recent evidence has strengthened the case that MYB is activated in colon and breast cancer.
Abstract: The transcription factor MYB has a key role as a regulator of stem and progenitor cells in the bone marrow, colonic crypts and a neurogenic region of the adult brain. It is in these compartments that a deficit in MYB activity leads to severe or lethal phenotypes. As was predicted from its leukaemogenicity in several animal species, MYB has now been identified as an oncogene that is involved in some human leukaemias. Moreover, recent evidence has strengthened the case that MYB is activated in colon and breast cancer: a block to MYB expression is overcome by mutation of the regulatory machinery in the former disease and by oestrogen receptor-alpha (ERalpha) in the latter.
560 citations
TL;DR: The current understandings of tumor stroma in breast cancer are summarized and the biologic markers to categorize patients into a specific and confirmed subtype for personalized treatment are described.
Abstract: Cancer is a systemic disease encompassing multiple components of both tumor cells themselves and host stromal cells. It is now clear that stromal cells in the tumor microenvironment play an important role in cancer development. Molecular events through which reactive stromal cells affect cancer cells can be defined so that biomarkers and therapeutic targets can be identified. Cancer-associated fibroblasts (CAFs) make up the bulk of cancer stroma and affect the tumor microenvironment such that they promote cancer initiation, angiogenesis, invasion, and metastasis. In breast cancer, CAFs not only promote tumor progression but also induce therapeutic resistance. Accordingly, targeting CAFs provides a novel way to control tumors with therapeutic resistance. This review summarizes the current understandings of tumor stroma in breast cancer with a particular emphasis on the role of CAFs and the therapeutic implications of CAFs. In addition, the effects of other stromal components such as endothelial cells, macrophages, and adipocytes in breast cancer are also discussed. Finally, we describe the biologic markers to categorize patients into a specific and confirmed subtype for personalized treatment.
559 citations