Role of Kindlin 2 in prostate cancer.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Prostatic Neoplasms*/metabolism ; Prostatic Neoplasms*/pathology ; Prostatic Neoplasms*/genetics ; Neoplasm Proteins*/metabolism ; Neoplasm Proteins*/genetics ; Membrane Proteins*/metabolism ; Membrane Proteins*/genetics ; Cell Adhesion*; Male ; Humans ; Animals ; Cell Line, Tumor ; Mice ; Cell Movement ; Cell Proliferation ; Integrins/metabolism

Kindlin-2 is a cytoskeletal adapter protein that is present in many different cell types. By virtue of its interaction with multiple binding partners, Kindlin-2 intercalates into numerous signaling pathways and cytoskeletal nodes. A specific interaction of Kindlin-2 that is of paramount importance in many cellular responses is its direct binding to the cytoplasmic tails of integrins, an interaction that controls many of the adhesive, migratory and signaling responses mediated by members of the integrin family of cell-surface heterodimers. Kindlin-2 is highly expressed in many cancers and is particularly prominent in prostate cancer cells. CRISPR/cas9 was used as a primary approach to knockout expression of Kindlin-2 in both androgen-independent and dependent prostate cancer cell lines, and the effects of Kindlin-2 suppression on oncogenic properties of these prostate cancer cell lines was examined. Adhesion to extracellular matrix proteins was markedly blunted, consistent with the control of integrin function by Kindlin-2. Migration across matrices was also affected. Anchorage independent growth was markedly suppressed. These observations indicate that Kindlin-2 regulates hallmark features of prostate cancer cells. In androgen expressing cells, testosterone-stimulated adhesion was Kindlin-2-dependent. Furthermore, tumor growth of a prostate cancer cell line lacking Kindlin-2 and implanted into the prostate gland of immunocompromised mice was markedly blunted and was associated with suppression of angiogenesis in the developing tumor. These results establish a key role of Kindlin-2 in prostate cancer progression and suggest that Kindlin-2 represents an interesting therapeutic target for treatment of prostate cancer.
(© 2024. The Author(s).)

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P30 CA010815 United States CA NCI NIH HHS; R35 CA220446 United States CA NCI NIH HHS

Keywords: Androgen dependence; Integrins; Kindlin-2; Prostate cancer; Tumor angiogenesis; Tumor progression

0 (Neoplasm Proteins)
0 (Membrane Proteins)
0 (FERMT2 protein, human)
0 (Integrins)

Date Created: 20240827 Date Completed: 20240827 Latest Revision: 20241210

20241210

PMC11349918

10.1038/s41598-024-70202-2

39191802