MASTL inhibition promotes mitotic catastrophe through PP2A activation to inhibit cancer growth and radioresistance in breast cancer cells.

Abstract

BACKGROUND:

Although MASTL (microtubule-associated serine/threonine kinase-like) is a key mitotic kinase that regulates mitotic progression through the inactivation of tumor suppressor protein phosphatase 2A (PP2A), the antitumor mechanism of MASTL targeting in cancer cells is still unclear.

METHODS:

MASTL expression was evaluated by using breast cancer tissue microarrays and public cancer databases. The effects of MASTL depletion with siRNAs were evaluated in various breast cancer cells or normal cells. Various methods, including cell viability, cell cycle, soft agar, immunoblotting, immunofluorescence, PP2A activity, live image, and sphere forming assay, were used in this study.

RESULTS:

This study showed the oncosuppressive mechanism of MASTL targeting that promotes mitotic catastrophe through PP2A activation selectively in breast cancer cells. MASTL expression was closely associated with tumor progression and poor prognosis in breast cancer. The depletion of MASTL reduced the oncogenic properties of breast cancer cells with high MASTL expression, but did not affect the viability of non-transformed normal cells with low MASTL expression. With regard to the underlying mechanism, we found that MASTL inhibition caused mitotic catastrophe through PP2A activation in breast cancer cells. Furthermore, MASTL depletion enhanced the radiosensitivity of breast cancer cells with increased PP2A activity. Notably, MASTL depletion dramatically reduced the formation of radioresistant breast cancer stem cells in response to irradiation.

CONCLUSION:

Our data suggested that MASTL inhibition promoted mitotic catastrophe through PP2A activation, which led to the inhibition of cancer cell growth and a reversal of radioresistance in breast cancer cells.

• Authors: Yi Na Yoon, Min Ho Choe, Kwan-Young Jung, Sang-Gu Hwang, Jeong Su Oh, Jae-Sung Kim
• Journal: BMC cancer (BMC Cancer) Vol. 18 Issue 1 Pg. 716 (Jul 05 2018) ISSN: 1471-2407 [Electronic] England
• PMID: 29976159 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• Microtubule-Associated Proteins
• Proto-Oncogene Proteins
• MASTL protein, human
• Protein Serine-Threonine Kinases
• Protein Phosphatase 2

Topics

• Breast Neoplasms (drug therapy, mortality, pathology, radiotherapy)
• Cell Cycle Proteins (antagonists & inhibitors)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Enzyme Activation
• Female
• Humans
• Microtubule-Associated Proteins (antagonists & inhibitors)
• Mitosis
• Neoplastic Stem Cells (radiation effects)
• Prognosis
• Protein Phosphatase 2 (physiology)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Proto-Oncogene Proteins (antagonists & inhibitors)
• Radiation Tolerance
• Polo-Like Kinase 1