Details

Autor(en) / Beteiligte

• Newman, Daniel
• Young, Lorna E.
• Waring, Thomas
• Brown, Louise
• Wolanska, Katarzyna I.
• MacDonald, Ewan
• Charles-Orszag, Arthur
• Goult, Benjamin T.
• Caswell, Patrick T.
• Sakuma, Tetsushi
• Yamamoto, Takashi
• Machesky, Laura M.
• Morgan, Mark R.
• Zech, Tobias

Titel

3D matrix adhesion feedback controls nuclear force coupling to drive invasive cell migration

Ist Teil von

• Cell reports (Cambridge), 2023-12, Vol.42 (12), p.113554-113554, Article 113554

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Cell invasion is a multi-step process, initiated by the acquisition of a migratory phenotype and the ability to move through complex 3D extracellular environments. We determine the composition of cell-matrix adhesion complexes of invasive breast cancer cells in 3D matrices and identify an interaction complex required for invasive migration. βPix and myosin18A (Myo18A) drive polarized recruitment of non-muscle myosin 2A (NM2A) to adhesion complexes at the tips of protrusions. Actomyosin force engagement then displaces the Git1-βPix complex from paxillin, establishing a feedback loop for adhesion maturation. We observe active force transmission to the nucleus during invasive migration that is needed to pull the nucleus forward. The recruitment of NM2A to adhesions creates a non-muscle myosin isoform gradient, which extends from the protrusion to the nucleus. We postulate that this gradient facilitates coupling of cell-matrix interactions at the protrusive cell front with nuclear movement, enabling effective invasive migration and front-rear cell polarity. [Display omitted] •3D cell-matrix adhesions share key nodes with 2D focal adhesions but have distinct features•Cancer cell invasion requires mechanical integration between adhesion sites and the nucleus•βPix and Myo18A are required to establish an NM2 isoform gradient between adhesions and nucleus•Actomyosin force engagement displaces Git-βPix-Myo18A, establishing a feedback loop Newman et al. define 3D cell-matrix adhesion composition and a pathway required for invasion in 3D matrix environments. βPix and Myo18A are required at cell adhesions to establish a polarized non-muscle myosin 2 isoform force-transduction network. This pathway is essential for nuclear movement and to drive cell migration through the matrix.