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1. Nollet, Eric A. Integrin alpha6 Activity in Castration-Resistant Prostate Cancer.

Degree: 2017, Van Andel Research Institute

Although castration-resistant prostate cancers no longer respond to anti-androgen therapies, the androgen receptor (AR) is still required to promote tumor survival. However, the signaling pathways downstream of AR that promote this survival are not well known. We recently identified an AR-dependent survival pathway whereby AR induction of integrin α6β1 and adhesion to laminin activates NF-κB/RelA signaling and Bcl-xL. This pathway acts in parallel with the PI3K/Akt pathway in Pten-null tumor cells such that combined inhibition of both PI3K and integrin α6β1 is required to effectively kill tumor cells adherent to laminin. However, PTEN-null castration-resistant tumors were not effectively killed by this combination. I discovered that BNIP3, a hypoxia-induced BH3-only, pro-mitophagic Bcl-2 family member, is induced by androgen in castration-resistant cells through integrin α6β1 and HIF1α. Furthermore, castration-resistant cells adherent to laminin were much more efficient at inducing autophagy in response to androgen. Androgen blocked the ability of the PI3K inhibitor PX866 to kill castration-resistant tumors, but this was reversed by loss of BNIP3. Although BNIP3 was dispensable for androgen-induced autophagy, its mitophagy function was required for BNIP3 to promote resistance to PX866. Thus, enhanced hypoxia signaling in cooperation with AR/α6β1/HIF1α signaling on laminin in castration-resistant cells drives the expression of BNIP3 and enhances autophagy, both of which contribute to PX866 resistance through induction of mitophagy.

Subjects/Keywords: Molecular biology; Cellular biology; Oncology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Nollet, E. A. (2017). Integrin alpha6 Activity in Castration-Resistant Prostate Cancer. (Thesis). Van Andel Research Institute. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10289534

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Nollet, Eric A. “Integrin alpha6 Activity in Castration-Resistant Prostate Cancer.” 2017. Thesis, Van Andel Research Institute. Accessed October 24, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10289534.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Nollet, Eric A. “Integrin alpha6 Activity in Castration-Resistant Prostate Cancer.” 2017. Web. 24 Oct 2017.

Vancouver:

Nollet EA. Integrin alpha6 Activity in Castration-Resistant Prostate Cancer. [Internet] [Thesis]. Van Andel Research Institute; 2017. [cited 2017 Oct 24]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10289534.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nollet EA. Integrin alpha6 Activity in Castration-Resistant Prostate Cancer. [Thesis]. Van Andel Research Institute; 2017. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10289534

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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