Related Experiment Video

Updated: Aug 10, 2025

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

624

EHBP1L1 Drives Immune Evasion in Renal Cell Carcinoma through Binding and Stabilizing JAK1

Yihui Pan1,2, Guannan Shu1, Liangmin Fu1

  • 1Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 13, 2023
PubMed

Insights

EH domain-binding protein 1-like protein 1 (EHBP1L1) drives immune evasion in renal cell carcinoma (RCC) by stabilizing JAK1. Inhibiting EHBP1L1 enhances anti-tumor immunity and improves immune checkpoint blockade therapy efficacy in RCC.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Renal cell carcinoma (RCC) features an immunosuppressive tumor microenvironment (TME) hindering effective immune attack.
  • Understanding tumor immune evasion mechanisms and identifying novel therapeutic targets are critical for enhancing immune checkpoint blockade (ICB) efficacy in RCC.

Purpose of the Study:

  • To elucidate the role of EH domain-binding protein 1-like protein 1 (EHBP1L1) in the IFN-γ/JAK/STAT signaling pathway within the RCC TME.
  • To investigate EHBP1L1 as a potential therapeutic target to overcome ICB resistance in RCC.

Main Methods:

  • Identification of EHBP1L1 as a mediator in IFN-γ/JAK1/STAT1/PD-L1 signaling in RCC.
  • Analysis of EHBP1L1 expression correlation with prognosis and ICB response in RCC.
  • Assessment of EHBP1L1 depletion effects on tumor growth and CD8+ T cell immunity.
  • Mechanistic studies on EHBP1L1 interaction with JAK1 and its impact on JAK1 stability and signaling.
  • Evaluation of combined EHBP1L1 inhibition and ICB therapy in RCC patient-derived xenograft (PDX) models.

Main Results:

  • EHBP1L1 is highly expressed in RCC, correlating with poor prognosis and ICB resistance.
  • EHBP1L1 depletion significantly inhibits RCC tumor growth by enhancing CD8+ T cell-mediated immunity.
  • EHBP1L1 stabilizes JAK1 by preventing proteasomal degradation, thereby activating JAK1/STAT1/PD-L1 signaling and promoting an immunosuppressive TME.
  • Combination therapy of EHBP1L1 inhibition and ICB effectively reprograms the TME, prevents immune evasion, and enhances therapeutic efficacy in RCC PDX models.

Conclusions:

  • EHBP1L1 plays a critical role in mediating immune evasion in RCC through the JAK1/STAT1/PD-L1 pathway.
  • EHBP1L1 represents a promising therapeutic target, potentially complementing ICB therapy for improved outcomes in RCC patients.
Keywords:
EHBP1L1IFN-γ/JAK1/STAT1/PD-L1 signalingimmune evasionrenal cell carcinoma

More Related Videos

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection10:15

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection

Published on: November 10, 2021

1.9K
Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue10:11

Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue

Published on: January 3, 2013

23.2K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.8K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.3K