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MYO10-filopodia support basement membranes at pre-invasive tumor boundaries. | LitMetric

MYO10-filopodia support basement membranes at pre-invasive tumor boundaries.

Dev Cell

Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, University of Turku, 20520 Turku, Finland; Department of Life Technologies, University of Turku, 20520 Turku, Finland; Western Finnish Cancer Center (FICAN West), University of Turku, FI-20520 Turku, Finland; Foundation for the Finnish Cancer Institute, Tukholmankatu 8, FI-00014 Helsinki, Finland. Electronic address:

Published: October 2022

AI Article Synopsis

  • Ductal carcinoma in situ (DCIS) is a non-invasive precursor to breast cancer, where tumor cells start to invade surrounding tissues after compromising the protective basement membrane.
  • Myosin-X (MYO10) has been found to be elevated in both DCIS and invasive breast cancer, suggesting a role in cancer progression and cell invasion.
  • Interestingly, while MYO10 facilitates cell movement and invasion at advanced stages, it appears to play a protective role in early-stage breast cancer by helping maintain the integrity of the basement membrane and limiting tumor spread.

Article Abstract

Ductal carcinoma in situ (DCIS) is a pre-invasive stage of breast cancer. During invasion, the encapsulating DCIS basement membrane (BM) is compromised, and tumor cells invade the surrounding stroma. The mechanisms that regulate functional epithelial BMs in vivo are poorly understood. Myosin-X (MYO10) is a filopodia-inducing protein associated with metastasis and poor clinical outcome in invasive breast cancer (IBC). We identify elevated MYO10 expression in human DCIS and IBC, and this suggests links with disease progression. MYO10 promotes filopodia formation and cell invasion in vitro and cancer-cell dissemination from progressively invasive human DCIS xenografts. However, MYO10-depleted xenografts are more invasive. These lesions exhibit compromised BMs, poorly defined borders, and increased cancer-cell dispersal and EMT-marker-positive cells. In addition, cancer spheroids are dependent on MYO10-filopodia to generate a near-continuous extracellular matrix boundary. Thus, MYO10 is protective in early-stage breast cancer, correlating with tumor-limiting BMs, and pro-invasive at later stages, facilitating cancer-cell dissemination.

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Source
http://dx.doi.org/10.1016/j.devcel.2022.09.016DOI Listing

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