Related Experiment Video

Updated: Sep 19, 2025

The Soft Agar Colony Formation Assay
08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

112.3K

Blocking the functional domain of cancer cell surface TIP1 upregulates Midkine via the β-catenin/Wnt signaling

Minakshi Saikia1, Harendra Kumar Shah1, Dennis E Hallahan1,2

  • 1Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.

Cancer Gene Therapy
|June 18, 2025
PubMed

Insights

Targeting Tax interacting Protein-1 (TIP1) and Midkine (MDK) may overcome drug resistance in non-small cell lung cancer (NSCLC). Blocking TIP1 increases MDK, which cancer cells use to resist treatment, suggesting a combined therapeutic approach for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Drug resistance in cancer limits therapeutic success, particularly in non-small cell lung cancer (NSCLC).
  • New strategies are needed to improve treatment efficacy for NSCLC patients.
  • Tax interacting Protein-1 (TIP1) is a radiation-inducible target implicated in cancer, with its expression linked to poor NSCLC outcomes.

Purpose of the Study:

  • To investigate the role of TIP1 in NSCLC and its interaction with other molecular pathways.
  • To explore the potential of targeting TIP1 and Midkine (MDK) as a combined therapeutic strategy for NSCLC.

Main Methods:

  • Antibody-mediated blockade of TIP1's functional domain.
  • Proteomic analysis to identify molecular changes post-TIP1 inhibition.
  • Investigation of Wnt signaling pathway activation and β-catenin involvement.
  • Genetic silencing of β-catenin.
  • Assessing the effect of combined TIP1 and MDK inhibition on cancer cell proliferation and colony formation.

Main Results:

  • Antibody blockade of TIP1 reduced NSCLC cell proliferation and increased sensitivity to radiation.
  • TIP1 blockade led to a ten-fold increase in Midkine (MDK) expression.
  • Wnt signaling activation mediated MDK upregulation following TIP1 blockade, dependent on β-catenin.
  • Simultaneous inhibition of TIP1 and MDK significantly reduced cancer cell colony-forming ability.

Conclusions:

  • MDK upregulation appears to be a resistance mechanism employed by cancer cells against TIP1-targeted therapy.
  • Co-targeting cell surface TIP1 and MDK presents a promising therapeutic strategy for improving outcomes in NSCLC patients.

More Related Videos

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics08:11

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics

Published on: March 26, 2018

8.5K
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

14.1K

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
9.0K
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...
2.2K
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...
3.9K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.4K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.4K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K