β1A Integrin Expression Is Required for Type 1 Insulin-Like Growth Factor Receptor Mitogenic and Transforming Activities and Localization to Focal Contacts
10.1158/0008-5472.can-04-4315
Crossref journal-article
American Association for Cancer Research (AACR)
Cancer Research (1086)
Abstract

Abstract The cells' ability to proliferate in response to growth factor stimulation is significantly altered during cancer progression. To investigate the mechanisms underlying these alterations in prostate cancer, the role and expression of β1A integrin and type 1 insulin-like growth factor receptor (IGF-IR), known to contribute to cell proliferation and transformation, were analyzed. Using small interfering RNA oligonucleotides to down-regulate β1A, we show that β1A expression is required for IGF-IR–mediated prostate cancer cell proliferation and anchorage-independent growth. In vivo, using age-matched transgenic adenocarcinoma of mouse prostate (TRAMP) mice at different stages of prostate cancer [prostatic intraepithelial neoplasia, PIN; well-differentiated adenocarcinoma, WD; and poorly differentiated adenocarcinoma, PD], the expression of β1A and of IGF-IR was studied. β1A and IGF-IR expression levels were concurrently up-regulated in high PIN and WD, whereas their expression did not correlate in late-stage PD. In contrast to the up-regulated expression of β1A, the levels of β1C, a β1 cytoplasmic variant that inhibits cell proliferation, were down-regulated in all stages of prostate cancer. A similar expression pattern was observed for a β1C downstream effector, Grb2-associated binder-1 (Gab1) which is known to inhibit IGF-IR phosphorylation. To analyze in vitro the mechanistic implications of β1A, β1C, and Gab1 deregulation in prostate cancer, we investigated whether expression of either β1 variant in β1-null cells affected IGF-IR localization. We found that IGF-IR and β1A were colocalized in highly specialized integrin signaling compartments, designated focal contacts. However, in the presence of β1C, IGF-IR remained diffuse on the cell surface and did not localize to focal contacts. The findings that β1 integrins and IGF-IR are concurrently deregulated and that expression of β1 integrins is necessary to achieve appropriate IGF-IR intracellular distribution point to the important role that the cross-talk between these receptors may have during prostate cancer progression and will be helpful in formulating new therapeutic strategies.

Bibliography

Goel, H. L., Breen, M., Zhang, J., Das, I., Aznavoorian-Cheshire, S., Greenberg, N. M., Elgavish, A., & Languino, L. R. (2005). β1A Integrin Expression Is Required for Type 1 Insulin-Like Growth Factor Receptor Mitogenic and Transforming Activities and Localization to Focal Contacts. Cancer Research, 65(15), 6692–6700.

Authors 8
  1. Hira Lal Goel (first)
  2. Michael Breen (additional)
  3. Jianzhong Zhang (additional)
  4. Ishita Das (additional)
  5. Sadie Aznavoorian-Cheshire (additional)
  6. Norman M. Greenberg (additional)
  7. Ada Elgavish (additional)
  8. Lucia R. Languino (additional)
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Dates
Type When
Created 19 years, 11 months ago (Sept. 15, 2005, 6:03 p.m.)
Deposited 2 years, 7 months ago (Jan. 11, 2023, 4:29 p.m.)
Indexed 1 year, 1 month ago (July 23, 2024, 7:59 a.m.)
Issued 20 years ago (Aug. 1, 2005)
Published 20 years ago (Aug. 1, 2005)
Published Online 20 years ago (Aug. 1, 2005)
Published Print 20 years ago (Aug. 1, 2005)
Funders 0

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@article{Goel_2005, title={β1A Integrin Expression Is Required for Type 1 Insulin-Like Growth Factor Receptor Mitogenic and Transforming Activities and Localization to Focal Contacts}, volume={65}, ISSN={1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.can-04-4315}, DOI={10.1158/0008-5472.can-04-4315}, number={15}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Goel, Hira Lal and Breen, Michael and Zhang, Jianzhong and Das, Ishita and Aznavoorian-Cheshire, Sadie and Greenberg, Norman M. and Elgavish, Ada and Languino, Lucia R.}, year={2005}, month=aug, pages={6692–6700} }