The nonreceptor tyrosine kinase Pyk2 is highly expressed in invasive breast cancer, but how it potentiates tumor cell invasiveness is unclear. Genna et al. find that Pyk2 and the closely related kinase FAK modulate breast cancer cell invasiveness by distinct mechanisms and coordinate the balance between focal adhesion–mediated migration and invadopodia-dependent extracellular matrix invasion.
Metastatic dissemination of cancer cells from the primary tumor and their spread to distant sites in the body is the leading cause of mortality in breast cancer patients. While researchers have identified treatments that shrink or slow metastatic tumors, no treatment that permanently eradicates metastasis exists at present. Here, we show that the ABL kinase inhibitors imatinib, nilotinib, and GNF-5 impede invadopodium precursor formation and cortactin-phosphorylation dependent invadopodium maturation, leading to decreased actin polymerization in invadopodia, reduced extracellular matrix degradation, and impaired matrix proteolysis-dependent invasion. Using a mouse xenograft model we demonstrate that, while primary tumor size is not affected by ABL kinase inhibitors, the in vivo matrix metalloproteinase (MMP) activity, tumor cell invasion, and consequent spontaneous metastasis to lungs are significantly impaired in inhibitor-treated mice. Further proteogenomic analysis of breast cancer patient databases revealed co-expression of the Abl-related gene (Arg) and cortactin across all hormone- and human epidermal growth factor receptor 2 (HER2)-receptor status tumors, which correlates synergistically with distant metastasis and poor patient prognosis. Our findings establish a prognostic value for Arg and cortactin as predictors of metastatic dissemination and suggest that therapeutic inhibition of ABL kinases may be used for blocking breast cancer metastasis.
Cilj istraživanja je bila procena posturalnog statusa dece mlađeg školskog uzrasta Osnovne škole "Ivo Lola Ribar" iz Novog Sada. Uzorak ispitanika čini 61 učenik prvog razreda, 33 dečaka i 28 devojčica hronološke starosti 8,5 godine. Za procenu posturalnog statusa primenjena je modifikovana vizuelna metoda Napoleona Volanskog. Rezultati istraživanja pokazuju da ispitanici nemaju znatno odstupanje od dobrog držanja tela kada su u pitanju kifo-lordoza i ravna leđa, a dijagnostikovana su kako mala tako i znatna odstupanja od dobrog držanja kod kifotičnog i lordotičnog lošeg držanja tela. U odnosu na pol, dobro držanje ima 84,8 % dečaka, što je manje od devojčica-92,9 %. Kod posturalnih poremećaja u frontalnoj ravni najzastupljenija je desna grudna skolioza gde je nadjena statistički značajna razlika između polova. Kod deformiteta grudnog koša dominirale su izdubljene grudi (pectus excavatus)-83,6%. Najmanje zastupljen poremećaj grudnog koša u ispitivanom uzorku su ispupčene grudi (pectus carinatus). Razlike u polu nisu statistički značajne. Najzastupljeniji posturalni poremećaj nogu u ukupnom uzorku ispitanika su " X" noge (Genu valgum), bez statitički značajne razlike u polnoj strukturi. Najmanje zastupljen posturalni poremećaj nogu bio je "O" noge (Genu varum
Core stability has a very positive effect on the prevention of lumbar lordosis and lower back pain. The main focus of this paper was on a review of the available literature on the influence of trunk stability on lower back pain and lumbar lordosis. The two electronic databases researched for collecting articles are PubMed and ScienceDirect. A search was conducted by title, taking a predefined combination of the following keywords into account: low back pain, core stability, training, sports. Screening processes are summarized through a PRISMA flow chart. 408 studies were identified, of which 20 met the inclusion criteria. It was concluded that exercise on the stability of the pelvic nucleus and muscles is recommended as the simplest and most favorable prevention of lower back pain and lumbar lordosis. The stability of the nucleus helps to overcome the main causes and deprive the body of functional disorders and pain.
Saţetak.Istraživanje je sprovedeno na uzorku od 62 ispitanik, uzrasta 7 godina iz Koceljeve (M=31, F=31) sa ciljem doprinosa boljem razumevanju potencijalnih faktora koji se mogu dovesti u vezu sa nastajanjem lošeg telesnog držanja segmenata tela i bolje prevencije meĎu populacijom dece mlaĎeg školskog uzrasta. Roditelji su popunjavali nestandardizovan upitnik konstruisan za potrebe istraživanja. Rezultati ukazuju da je oko petine ispitanika aktivno svih sedam dana u nedelji po 20-30 minuta, da čak 80.6% koristi računar u svojoj kući u nekom obliku, a najviše vremena vikendomod, 1-2 časa dnevno. UtvrĎene su statistički značajne korelacije životnih navika i stanja segmenata posturalnog statusa kod dece muškog i ženskog pola. Prisutna je razvijena svest roditelja o potrebi fizičke aktivnosti kod dece sa narušenim posturalnim poremećajima koji se odnose na ravna stopala i deformitete kičme (kifoza, leva grudna skolioza i kompenzatorna skolioza). Kao indikatori lošeg stanja držanja posturalnih segmenata može se istaći korišćenje računara i zastupljenost gledanja tv-a.
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