Novel kinase regulators of extracellular matrix internalisation identified by high-content screening modulate invasive carcinoma cell migration.

The interaction between cancer cells and the extracellular matrix (ECM) plays a pivotal role in tumour progression. While the extracellular degradation of ECM proteins has been well characterised, ECM endocytosis and its impact on cancer cell progression, migration, and metastasis is poorly understood. ECM internalisation is increased in invasive breast cancer cells, suggesting it may support invasiveness.

A series of two-photon absorption pyridinium sulfonate inner salts targeting endoplasmic reticulum (ER), inducing cellular stress and mitochondria-mediated apoptosis in cancer cells.

In this study, a two-photon active DiphenthioER1 was screened from the four pyridinium sulfonate salt derivatives (TriphenER1-2 and DiphenthioER1-2) for imaging endoplasmic reticulum (ER) and tracking the dynamics of the ER morphology. The photophysical properties of TriphenER1-2 and DiphenthioER1-2 were systemically investigated both experimentally and theoretically, revealing that they possess large Stokes shifts, and large two-photon absorption cross-sections from 163 GM to 2023 GM in the near infrared region using a Z-scan method by avoiding spontaneous fluorescence, deep tissue penetration, and low cell damage in living cells. Among them, the DiphenthioER1 compound was found to exhibit the highest cellular uptake ability and two-photon fluorescence signals using confocal microscopy.