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Novel use of TGF (Transforming Growth Facto)-beta receptor binding protein-1

A TGF- and protein-binding technology, used in drug combinations, introduction of foreign genetic material using vectors, cells modified by introduction of foreign genetic material, etc.

Active Publication Date: 2014-02-05
SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The regulation of TRIP-1 in cell growth has obtained some research results, but whether TRIP-1 plays a role in the process of tumor cell migration is rarely reported

Method used

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  • Novel use of TGF (Transforming Growth Facto)-beta receptor binding protein-1
  • Novel use of TGF (Transforming Growth Facto)-beta receptor binding protein-1
  • Novel use of TGF (Transforming Growth Facto)-beta receptor binding protein-1

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Example 1. Application of substances that reduce the expression level of TRIP-1 in the preparation of reagents that increase the phosphorylation level of Ezrin and / or reagents that promote the generation of cellular filopodia

[0080] The amino acid sequence of TGF-β receptor binding protein-1 (TRIP-1) is shown in SEQ ID No.2, its coding sequence is shown in SEQ ID No.1; the amino acid sequence of Ezrin is shown in SEQ ID As shown in No.4, its coding sequence is shown in SEQ ID No.3.

[0081] Significant co-localization of Ezrin and TRIP-1 at the pseudopodia of cell migration ( figure 2 A and B, arrows), indicating that TRIP-1 may affect cell migration by inhibiting the transfer of Ezrin to migrating protrusions. Next, the inventors investigated how loss of TRIP-1 would affect cell migration. First, experiments showed that TRIP-1-specific siRNAs (siRNA#1, siRNA#2, siRNA#3, siRNA mix1 and siRNA mix2) had higher knockdown efficiencies ( image 3 Middle A). It is wort...

Embodiment 2

[0094] Example 2. Application of Substances Regulating the Expression Level of TGF-β Receptor Binding Protein-1 in the Preparation of Reagents Regulating Cell Adhesion and / or Migration

[0095] Filopodia are a critical step in cell motility, directly affecting cell adhesion and migration. Next, the function of TRIP-1 in cell adhesion and migration was investigated. Adhesion assay and Transwell chamber method showed that the adhesion ability of TRIP-1 knockout cells ( Figure 4 in A) and migratory ability ( Figure 4 Middle B) are significantly enhanced. In order to verify whether TRIP-1 can inhibit the cell migration promoted by Ezrin, a wound healing experiment was performed. The results showed that in HeLa cells, increasing the expression of TRIP-1 could inhibit the cell migration induced by Ezrin expression ( Figure 4 Middle C). It shows that the substance regulating the expression level of TGF-β receptor binding protein-1 can be used to prepare a reagent for regulati...

Embodiment 3

[0100] Example 3. Substances that increase the expression level of TGF-β receptor binding protein-1 are prepared to inhibit Cdc42 L61 Use of reagents that promote filopodia formation, cell adhesion and / or migration

[0101] Cdc42 L61 It is a crucial factor regulating the formation of filopodia (Lamarche N, Tapon N, Stowers L, Burbelo PD, Bridges T, Chant J, Hall A. Rac and Cdc42induce actin polymerization and G1cell cycle progression independently of p65PAK and the JNK / SAPK MAP kinase cascade. Cell.1996Nov1;87(3):519-29;Nobes CD, Hall A.Rho , rac, and cdc42GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 1995Apr7;81(1):53-62).

[0102] Although the reduction of TRIP-1 can make cells generate filopodia, it is next to explore whether the overexpression of TRIP-1 can inhibit Cdc42 L61 Induced filopodia formation.

[0103] Transfect HeLa cells with pEYFP-N1 (empty vector) alone to obtain re...

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Abstract

The invention discloses a novel use of TGF (Transforming Growth Facto)-beta receptor binding protein-1. The novel use of TGF-beta receptor binding protein-1 provided by the invention comprises A and B: A. an application of substance used for regulating and controlling the expression level of the TGF-beta receptor binding protein-1 in preparation of a reagent used for regulating and controlling cell adhesion and / or migration; and B. an application of substance used for regulating and controlling the expression level of the TGF-beta receptor binding protein-1 in preparation of a reagent used for regulating and controlling filiform cell pseudopodia formation. In practical application, interaction of TRIP-1 and Ezrin can be used as a target site to inhibit or treat neoplasm metastasis; the TGF-beta can be used for regulating and controlling TRIP-1 and Ezrin cell membrane colocalization to treat the neoplasm metastasis; and the TRIP-l expression can be regulated and controlled to regulate Ezrin phosphorylation to treat the neoplasm metastasis.

Description

technical field [0001] The present invention relates to a new application of TGF-beta receptor binding protein-1. Background technique [0002] Ezrin (Ezrin) is an important member of the ERM (Ezrin / Radixin / Moesin) family. It is a connecting protein between the cytoskeleton and the cell membrane, and plays a structural and functional role in the integration and stability of the cell membrane region. Ezrin protein is involved in the formation of microvilli and the maintenance of cell shape, cell movement and adhesion, remodeling of the cytoskeleton and cell signal transduction process, and can be used as a membrane organism and connector to connect the cell membrane and the cytoskeleton, such as: with the cell membrane Molecules CD43, CD44, E-cadsdherin, ICAM-1, etc., and the cytoskeleton member F-actin (F-actin), and there are compelling clinical evidences that: Ezrin protein family and adhesion molecules in the control of cancer Cell functions such as adhesion and the biol...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P35/04C12N15/113C12N15/85C12N5/10
Inventor 黄来强万骏张宏玲王婧葛远龙
Owner SHENZHEN GRADUATE SCHOOL TSINGHUA UNIV
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