Stathmin is required for normal mouse mammary gland development and D16Her2-driven tumorigenesis

Ilenia Segatto, Mara De Marco Zompit, Francesca Citron, Sara D'Andrea, Gian Luca Rampioni Vinciguerra, Tiziana Perin, Stefania Berton, Giorgia Mungo, Monica Schiappacassi, Cristina Marchini, Augusto Amici, Andrea Vecchione, Gustavo Baldassarre, Barbara Belletti

Research output: Contribution to journalArticle

Abstract

Postnatal development of the mammary gland relies on the maintenance of oriented cell division and apicobasal polarity, both of which are often deregulated in cancer. The microtubule (MT) network contributes to control these processes; however, very little is known about the impact of altered MT dynamics in the development of a complex organ and on the role played by MT-interacting proteins such as stathmin. In this study, we report that female stathmin knockout (STM KO) mice are unable to nurse their litters due to frank impairment of mammary gland development. In mouse mammary epithelial cells, loss of stathmin compromised the trafficking of polarized proteins and the achievement of proper apicobasal polarity. In particular, prolactin receptor internalization and localization was altered in STM KO mammary epithelial cells, leading to decreased protein stability and downmodulation of the Prl/PrlR/STAT5 signaling pathway. Absence of stathmin induced alterations in mitotic spindle orientation, accumulation of mitotic defects, and apoptosis, overall contributing to tissue disorganization and further decreasing the expansion of the mammary epithelial compartment. Loss of stathmin in MMTV-D16HER2 transgenic mice decreased the incidence and increased the latency of these very aggressive mammary carcinomas. Collectively, these data identify the essential mammary protein stathmin as protumorigenic and suggest it may serve as a potential therapeutic target in breast cancer. Significance: Stathmin expression is critical to maintain oriented cell division and apicobasal polarity in normal mammary glands and to establish a protumorigenic program that eventually sustains HER2-positive breast cancer formation in mice.

Original languageEnglish
Pages (from-to)397-409
Number of pages13
JournalCancer Research
Volume79
Issue number2
DOIs
Publication statusPublished - Jan 15 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Segatto, I., De Marco Zompit, M., Citron, F., D'Andrea, S., Vinciguerra, G. L. R., Perin, T., Berton, S., Mungo, G., Schiappacassi, M., Marchini, C., Amici, A., Vecchione, A., Baldassarre, G., & Belletti, B. (2019). Stathmin is required for normal mouse mammary gland development and D16Her2-driven tumorigenesis. Cancer Research, 79(2), 397-409. https://doi.org/10.1158/0008-5472.CAN-18-2488