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Integrin α6A splice variant regulates proliferation and the Wnt/β-catenin pathway in human colorectal cancer cells.

Groulx JF, Giroux V, Beauséjour M, Boudjadi S, Basora N, Carrier JC, Beaulieu JF - Carcinogenesis (2014)

Bottom Line: The α6A silencing was also found to be associated with a significant repression of a number of Wnt/β-catenin pathway end points.Moreover, it was accompanied by a reduction in the capacity of these cells to develop tumours in xenografts.Taken together, these results demonstrate that the α6A variant is a pro-proliferative form of the α6 integrin subunit in CRC cells and appears to mediate its effects through the Wnt/β-catenin pathway.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology and Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.

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Knocked down α6A splice variant decreases cell proliferation. (A) Cell counts over a 3–6 day period after the seeding of Caco-2/15, DLD-1, T84 and HT29 stably expressing shα6A or shctl. Cells were counted at the indicated times. (B) BrdU labelling assay in Caco-2/15, DLD-1, T84 and HT29 shα6A and shctl cells at 2 days post-seeding. (C) ISEL assay in Caco-2/15, DLD-1, T84 and HT29 shα6A and shctl cells at 2 days post-seeding. Cytochalasin D (CD)-treated cells were used as positive control for apoptosis. Statistical analysis between shctrl and shα6A: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, t-test, n = 3.
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Figure 3: Knocked down α6A splice variant decreases cell proliferation. (A) Cell counts over a 3–6 day period after the seeding of Caco-2/15, DLD-1, T84 and HT29 stably expressing shα6A or shctl. Cells were counted at the indicated times. (B) BrdU labelling assay in Caco-2/15, DLD-1, T84 and HT29 shα6A and shctl cells at 2 days post-seeding. (C) ISEL assay in Caco-2/15, DLD-1, T84 and HT29 shα6A and shctl cells at 2 days post-seeding. Cytochalasin D (CD)-treated cells were used as positive control for apoptosis. Statistical analysis between shctrl and shα6A: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, t-test, n = 3.

Mentions: As the α6 integrin subunit was reported to be involved in cell proliferation (20,21), we further investigated if this function could be attributed to the α6A splice variant. Therefore, the involvement of the α6A variant in cancer cell growth was first assessed by establishing a growth curve using CRC cell populations knocked down for α6A, but expressing α6B, in vitro. As shown in Figure 3A, a significant reduction in cell number was observed throughout the culture beginning as early as 2 days post-seeding for T84, HT29 and DLD-1 shα6A cells in comparison with shctl cells and at 4 days for Caco-2/15 shα6A cells. Overall, abolition of the α6A subunit led to a significant and sustained reduction of the growth rate in all CRC cells tested.


Integrin α6A splice variant regulates proliferation and the Wnt/β-catenin pathway in human colorectal cancer cells.

Groulx JF, Giroux V, Beauséjour M, Boudjadi S, Basora N, Carrier JC, Beaulieu JF - Carcinogenesis (2014)

Knocked down α6A splice variant decreases cell proliferation. (A) Cell counts over a 3–6 day period after the seeding of Caco-2/15, DLD-1, T84 and HT29 stably expressing shα6A or shctl. Cells were counted at the indicated times. (B) BrdU labelling assay in Caco-2/15, DLD-1, T84 and HT29 shα6A and shctl cells at 2 days post-seeding. (C) ISEL assay in Caco-2/15, DLD-1, T84 and HT29 shα6A and shctl cells at 2 days post-seeding. Cytochalasin D (CD)-treated cells were used as positive control for apoptosis. Statistical analysis between shctrl and shα6A: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, t-test, n = 3.
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Related In: Results  -  Collection

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Figure 3: Knocked down α6A splice variant decreases cell proliferation. (A) Cell counts over a 3–6 day period after the seeding of Caco-2/15, DLD-1, T84 and HT29 stably expressing shα6A or shctl. Cells were counted at the indicated times. (B) BrdU labelling assay in Caco-2/15, DLD-1, T84 and HT29 shα6A and shctl cells at 2 days post-seeding. (C) ISEL assay in Caco-2/15, DLD-1, T84 and HT29 shα6A and shctl cells at 2 days post-seeding. Cytochalasin D (CD)-treated cells were used as positive control for apoptosis. Statistical analysis between shctrl and shα6A: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, t-test, n = 3.
Mentions: As the α6 integrin subunit was reported to be involved in cell proliferation (20,21), we further investigated if this function could be attributed to the α6A splice variant. Therefore, the involvement of the α6A variant in cancer cell growth was first assessed by establishing a growth curve using CRC cell populations knocked down for α6A, but expressing α6B, in vitro. As shown in Figure 3A, a significant reduction in cell number was observed throughout the culture beginning as early as 2 days post-seeding for T84, HT29 and DLD-1 shα6A cells in comparison with shctl cells and at 4 days for Caco-2/15 shα6A cells. Overall, abolition of the α6A subunit led to a significant and sustained reduction of the growth rate in all CRC cells tested.

Bottom Line: The α6A silencing was also found to be associated with a significant repression of a number of Wnt/β-catenin pathway end points.Moreover, it was accompanied by a reduction in the capacity of these cells to develop tumours in xenografts.Taken together, these results demonstrate that the α6A variant is a pro-proliferative form of the α6 integrin subunit in CRC cells and appears to mediate its effects through the Wnt/β-catenin pathway.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Intestinal Physiopathology, Department of Anatomy and Cell Biology and Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada.

Show MeSH
Related in: MedlinePlus