Factor quinolinone inhibitors alter cell morphology and motility by destabilizing interphase microtubules

Area of Science:

• Cell Biology
• Cancer Research
• Pharmacology

Background:

• Factor quinolinone inhibitors are identified as anti-cancer agents targeting the LSF (TFCP2) transcription factor.
• These compounds are known to disrupt mitotic spindles, contributing to anti-proliferative effects.

Purpose of the Study:

• To investigate the interphase effects of the lead compound FQI1 beyond its known role in mitosis.
• To elucidate the impact of FQI1 on microtubule dynamics, cell morphology, and motility in interphase cells.

Main Methods:

• Utilized two telomerase immortalized cell lines for experiments.
• Employed microtubule sedimentation assays and microscopy to assess microtubule network integrity.
• Observed cell morphology and motility changes following FQI1 treatment.
• Investigated the role of microtubule depolymerization in FQI1-induced cellular effects using taxol pretreatment.

Main Results:

• FQI1 rapidly disrupts the microtubule network, causing significant but incomplete microtubule depletion within minutes.
• Increased tubulin acetylation was observed on remaining microtubules shortly after FQI1 addition.
• FQI1 induced morphological alterations, including reduced cell spreading and increased cell circularity.
• FQI1 treatment decreased the rate and range of interphase cell locomotion, indicating impaired cell motility.

Conclusions:

• FQI1 interferes with crucial microtubule-associated functions during interphase, affecting cell morphology and motility.
• The disruption of the microtubule network by FQI1 has significant downstream consequences on cellular behavior.
• These findings expand the understanding of FQI1's mechanism of action as an anti-cancer compound.