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All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
09:55

All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System

Published on: December 20, 2021

The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion

Melanie Martini1, Alexandra Gnann, Daniela Scheikl

  • 1Department of Surgery, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.

The International Journal of Biochemistry & Cell Biology
|August 9, 2011
PubMed

Insights

The SASH1 protein, a tumor suppressor, regulates cancer cell adhesion and migration. Its interaction with cortactin influences actin cytoskeleton dynamics, impacting tumor growth and metastasis.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Signal adapter protein SASH1 (SLY-family) is a candidate tumor suppressor in breast and colon cancers.
  • Reduced SASH1 expression correlates with aggressive tumor growth, metastasis, and poor prognosis.
  • The precise biological function of SASH1 is largely unknown.

Purpose of the Study:

  • To elucidate the functional role of SASH1 in cancer.
  • To investigate the intracellular localization and protein interactions of SASH1.
  • To determine how SASH1 influences cancer cell behavior.

Main Methods:

  • Analysis of endogenous SASH1 intracellular localization.
  • Generation and study of structural SASH1 mutants.
  • Investigation of SASH1 interaction with cortactin.
  • Assessment of SASH1 effects on actin cytoskeleton, cell migration, and adhesion.

Main Results:

  • SASH1 localizes to the nucleus, cytoplasm, lamellipodia, and membrane ruffles, co-distributing with the actin cytoskeleton.
  • SASH1 interacts with the oncoprotein cortactin, a regulator of actin polymerization.
  • Increased SASH1 expression promotes filamentous actin content, cell protrusions, and elongated cell shape.
  • SASH1 inhibits cell migration and enhances cell adhesion to fibronectin and laminin.
  • Knock-down of SASH1 reduces cell-matrix adhesion.

Conclusions:

  • SASH1 plays a mechanistic role in tumor formation by regulating cancer cell adhesion and migration.
  • SASH1's function involves modulation of the actin cytoskeleton via interaction with cortactin.
  • SASH1 acts as a regulator of cell-matrix adhesion and cell motility.

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