Spindle misorientation in tumors from APC(min/+) mice
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Updated: Jun 26, 2026
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
Elizabeth S Fleming1, Maura Temchin, Qian Wu
1Center for Molecular Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA.
Abstract:
The adenomatous polyposis coli (APC) tumor suppressor gene is mutated in the majority of colon cancers, and its mutation may initiate cancer by multiple mechanisms. Recently, abnormal mitotic spindle orientation was shown in normal-appearing tissues from mice heterozygous for APC mutation. To determine the effect of APC mutation on spindle orientation in tumors, and to better understand its mechanism, we measured mitotic spindle orientation in intestinal tumors from APC mutant mice, with three-dimensionally reconstructed confocal stacks of microtubule immunofluorescence images. We found spindle angles were increased in crypts heterozygous for the APC(min) mutation, and further increased in tumors. Astral microtubules of these spindles were clearly evident, suggesting astral microtubule loss is not a major mechanism of spindle misorientation in intestinal cells lacking wild-type APC. beta-Catenin staining was markedly abnormal in crypts and tumors from the mutant mice, suggesting a possible role in spindle orientation. Spindle angles in colon tumors with wild-type APC were equivalent to those in wild-type mice, showing that spindle misorientation is specific to APC mutation and not a general feature of tumors. We suggest spindle misorientation may contribute to the loss of normal tissue organization during tumor formation and could offer new insights into early carcinogenic events.
Insights
Adenomatous polyposis coli (APC) gene mutations disrupt mitotic spindle orientation in intestinal cells, increasing angles in tumors. This APC mutation-specific misorientation may drive early cancer development and tissue disorganization.
Area of Science:
- Cell Biology
- Cancer Research
- Genetics
Background:
- The adenomatous polyposis coli (APC) gene is frequently mutated in colon cancers, potentially initiating tumorigenesis through various mechanisms.
- Previous studies indicated abnormal mitotic spindle orientation in normal tissues of APC-mutant mice.
Purpose of the Study:
- To investigate the impact of APC mutation on mitotic spindle orientation within intestinal tumors.
- To elucidate the underlying mechanisms of APC-driven spindle misorientation.
Main Methods:
- Three-dimensional reconstruction of confocal stacks using microtubule immunofluorescence imaging.
- Quantitative measurement of mitotic spindle angles in intestinal crypts and tumors from APC mutant mice.
Main Results:
- Spindle angles were significantly increased in intestinal crypts and tumors from APC mutant mice compared to wild-type controls.
- Abnormal beta-catenin staining was observed in APC mutant tissues, suggesting its potential involvement in spindle orientation.
- Spindle orientation in colon tumors with wild-type APC was normal, confirming specificity to APC mutation.
Conclusions:
- APC mutation leads to specific mitotic spindle misorientation in intestinal cells and tumors.
- Loss of astral microtubules is unlikely to be the primary cause of misorientation.
- Spindle misorientation may contribute to tissue disorganization during early stages of tumor formation, offering insights into carcinogenic events.
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