Muscle-specific deletion of SLK/Stk2 enhances p38 activity and myogenesis in mdx mice

Pryce, Benjamin R.; Labrèche, Cédrik; Hamoudi, Dounia; Abou-Hamad, John; Al-Zahrani, Khalid N.; Hodgins, Jonathan J.; Boulanger‐Piette, Antoine; Bossé, Sabrina; Balog-Alvarez, Cindy; Frenette, Jérôme; Ardolino, Michele; Kornegay, Joe N.; Sabourin, Luc A.

doi:10.1016/j.bbamcr.2020.118917

Cited by 5 publications

(4 citation statements)

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“…Tissues and cells were collected and homogenized in RIPA lysis buffer containing phosphatase and protease inhibitors as previously described [ 44 ]. The lysates were incubated at 4 °C with intermittent vortexing or multiple freeze/thaw cycles.…”

Section: Methodsmentioning

confidence: 99%

Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways

et al. 2021

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Background Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis. The expression of Postn in breast cancer cells has been correlated with a more aggressive phenotype. Despite extensive research, it remains unclear how epithelial cancer cells regulate Postn expression. Methods Using murine tumor models and human TMAs, we have assessed the proportion of tumor samples that have acquired Postn expression in tumor cells. Using biochemical approaches and tumor cell lines derived from Neu+ murine primary tumors, we have identified major regulators of Postn gene expression in breast cancer cell lines. Results Here, we show that, while the stromal compartment typically always expresses Postn, about 50% of breast tumors acquire Postn expression in the epithelial tumor cells. Furthermore, using an in vitro model, we show a cross-regulation between FGFR, TGFβ and PI3K/AKT pathways to regulate Postn expression. In HER2-positive murine breast cancer cells, we found that basic FGF can repress Postn expression through a PKC-dependent pathway, while TGFβ can induce Postn expression in a SMAD-independent manner. Postn induction following the removal of the FGF-suppressive signal is dependent on PI3K/AKT signaling. Conclusion Overall, these results reveal a novel regulatory mechanism and shed light on how breast tumor cells acquire Postn expression. This complex regulation is likely to be cell type and cancer specific as well as have important therapeutic implications.

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Section: Methodsmentioning

confidence: 99%

Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways

et al. 2021

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“…SLK deletion in vitro rescued myogenin induction in the presence of TGFβ, an inhibitory signal for myogenesis. COS-1 cells overexpressing SLK have been shown to activate p38 MAPKs (Hao et al, 2006), However, SLK deletion in muscle cells also activated p38 MAPKs and induced myogenin expression (Pryce et al, 2021). Together, these studies suggest that SLK may play a significant role in apoptosis-dependent physiological processes, such as in development and after injury, and that the therapeutic targeting of SLK might be beneficial for some renal and muscle pathologies (Cybulsky et al, 2009;Hao et al, 2006;Pryce et al, 2021).…”

Section: Slk In Cell Death and Injurymentioning

confidence: 99%

The Ste20-like kinase – a Jack of all trades?

Garland

Delisle

Al-Zahrani

et al. 2021

Journal of Cell Science

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Over the past 20 years, the Ste20-like kinase (SLK; also known as STK2) has emerged as a central regulator of cytoskeletal dynamics. Reorganization of the cytoskeleton is necessary for a plethora of biological processes including apoptosis, proliferation, migration, tissue repair and signaling. Several studies have also uncovered a role for SLK in disease progression and cancer. Here, we review the recent findings in the SLK field and summarize the various roles of SLK in different animal models and discuss the biochemical mechanisms regulating SLK activity. Together, these studies have revealed multiple roles for SLK in coupling cytoskeletal dynamics to cell growth, in muscle repair and in negative-feedback loops critical for cancer progression. Furthermore, the ability of SLK to regulate some systems appears to be kinase activity independent, suggesting that it may be an important scaffold for signal transduction pathways. These various findings reveal highly complex functions and regulation patterns of SLK in development and disease, making it a potential therapeutic target.

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“…Pharmacological inhibition of the BET proteins ameliorated muscle function by reducing oxidative stress (Segatto et al, 2020). Muscle-specific deletion of SLK enhances myogenic differentiation through up-regulation of myogenin in the mdx model (Pryce et al, 2021). Recent studies revealed stem cells as a new avenue of a potential treatment for DMD (Blau and Daley, 2019;Feige et al, 2018).…”

Section: Introductionmentioning

confidence: 99%