Jan Liphardt, Cal Berkeley, Mechanobiology of Tumor Progressoin

Question:

• Why are cell and tissue mechanics changed in virtually all cancers?
• Do the mechanical properties of cancer tumors drive tumor growth, or are they passive bystanders?
• Implications for diagnosis and therapy?

There exists geometrical modulation of oncogenic signaling:

• two cells, with identical number of progeins (and mRNAs) have entirely different phenotypes.
• related to intercellular networks

Tension homeostasis

• cells measure forces/compliance
• cell generate forces
• cells change compliance in response to changes in these
• Result: matrix stiffness promotes malignant progression (Levental et al., Cell (2009)
• Hardening can be reversed by LOX inhibitor, which reduces incidence and growth of tumors

Question: mutations related to cell adhesion/structure/firmness relevant to cancer?

• What combination of signals control cell shape?

Cancer book: Weinberg book (cancer diagram)

Question

• What are the difference in the info transfered across the nuclear membrane (proteins, DNA, RNA) between normal and cancer cells?
• Shape and size of nucleus is regulated during development and differentiation (unpublished data)
• Able to measure this info transfer using quantum dot networks on nuclear membrane