Integration of phosphoinositide 3-kinase (PI3K) and transforming growth factor β1 (TGF-β1) signaling cascades: role in the therapeutic inefficiency of tamoxifen

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Abstract

Growth factors signaling cascades and their interaction with the central regulatory targets of tumor cells and estrogens are considered as the main mechanisms of hormonal resistance in breast cancer. The integration  of the transforming growth factor β1 (TGF-β1) and PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) signaling pathway may result in the activation of proliferation and, as a result, the development of an in-effective response to therapy and disease progression. The review summarizes a systematic analysis of the literature data on the role of TGF-β1 signaling in the mechanisms of tamoxifen resistance to in the aspect of interaction  with the PI3K/Akt/mTOR. The interaction between the estrogen receptors α signaling and tamoxifen, the mechanisms of regulatory activation of TGF-β1 and PI3K/Akt/mTOR, as well as their contribution to the tamoxifen response are considered. The direct involvement of TGF-β1/PI3K in the mechanisms of tamoxifen resistance to determines the prospects for studying the effector of these cascades as molecular targets. The knowledge accumulated to date allows considering the TGF-β1/PI3K signaling pathway as a potential molecular tool for the search for effective strategies for blocking the resistance of tumor cells to tamoxifen.

About the authors

N. N. Babyshkina

Cancer Research Instituteof Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University

Author for correspondence.
Email: nbabyshkina@mail.ru
ORCID iD: 0000-0002-0562-3878

Nataliya N. Babyshkina.

5 Kooperativny Line, Tomsk 634009, Russia; 2 Moskovsky Trakt, Tomsk 634050

Russian Federation

 I.  A. Uzyanbaev

Siberian State Medical University

Email: fake@neicon.ru

2 Moskovsky Trakt, Tomsk 634050

Russian Federation

 T.  A. Dronova

Cancer Research Instituteof Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: fake@neicon.ru
ORCID iD: 0000-0003-3009-2404

5 Kooperativny Line, Tomsk 634009

Russian Federation

N. V. Cherdyntseva

Cancer Research Instituteof Tomsk National Research Medical Center of the Russian Academy of Sciences

Email: fake@neicon.ru
ORCID iD: 0000-0003-1526-9013

5 Kooperativny Line, Tomsk 634009

Russian Federation

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