ELIZA cgi-bash version rev. 1.91
- Medical English LInking keywords finder for the PubMed Zipped Archive (ELIZA) -

return kwic search for provide out of >500 occurrences
325270 occurrences (No.61 in the rank) during 5 years in the PubMed. [cache]
210) These data provide the first evidence that PEAK1 promotes tumorigenic phenotypes through a previously unrecognized SNAI2-PEAK1-INHBA stromal cell axis.
--- ABSTRACT ---
PMID:34239043 DOI:10.1038/s41388-021-01906-2
2021 Oncogene
* A SNAI2-PEAK1-INHBA stromal axis drives progression and lapatinib resistance in HER2-positive breast cancer by supporting subpopulations of tumor cells positive for antiapoptotic and stress signaling markers.
- Intercellular mechanisms by which the stromal microenvironment contributes to solid tumor progression and targeted therapy resistance remain poorly understood, presenting significant clinical hurdles. PEAK1 (Pseudopodium-Enriched Atypical Kinase One) is an actin cytoskeleton- and focal adhesion-associated pseudokinase that promotes cell state plasticity and cancer metastasis by mediating growth factor-integrin signaling crosstalk. Here, we determined that stromal PEAK1 expression predicts poor outcomes in HER2-positive breast cancers high in SNAI2 expression and enriched for MSC content. Specifically, we identified that the fibroblastic stroma in HER2-positive breast cancer patient tissue stains positive for both nuclear SNAI2 and cytoplasmic PEAK1. Furthermore, mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs) express high PEAK1 protein levels and potentiate tumorigenesis, lapatinib resistance and metastasis of HER2-positive breast cancer cells in a PEAK1-dependent manner. Analysis of PEAK1-dependent secreted factors from MSCs revealed INHBA/activin-A as a necessary factor in the conditioned media of PEAK1-expressing MSCs that promotes lapatinib resistance. Single-cell CycIF analysis of MSC-breast cancer cell co-cultures identified enrichment of p-Akthigh/p-gH2AXlow, MCL1high/p-gH2AXlow and GRP78high/VIMhigh breast cancer cell subpopulations by the presence of PEAK1-expressing MSCs and lapatinib treatment. Bioinformatic analyses on a PEAK1-centric stroma-tumor cell gene set and follow-up immunostaining of co-cultures predict targeting antiapoptotic and stress pathways as a means to improve targeted therapy responses and patient outcomes in HER2-positive breast cancer and other stroma-rich malignancies. These data provide the first evidence that PEAK1 promotes tumorigenic phenotypes through a previously unrecognized SNAI2-PEAK1-INHBA stromal cell axis.
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[frequency of next (right) word to provide]
(1)125 a (12)7 insight (23)3 sufficient (34)2 patients
(2)63 an (13)7 more (24)3 support (35)2 protection
(3)15 evidence (14)6 guidance (25)2 adequate (36)2 readers
(4)13 the (15)6 information (26)2 care (37)2 reasonable
(5)12 new (16)6 some (27)2 critical (38)2 reliable
(6)11 recommendations (17)5 novel (28)2 detailed (39)2 robust
(7)9 insights (18)4 better (29)2 direct (40)2 strong
(8)9 valuable (19)4 opportunities (30)2 greater (41)2 suggestions
(9)7 additional (20)4 useful (31)2 hypotheses (42)2 treatment
(10)7 further (21)3 practical (32)2 key
(11)7 important (22)3 researchers (33)2 mechanistic

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--- WordNet output for provide --- =>供給する, 与える, 規定する, 条件とする, 準備する, 用意する, 扶養する, 援助する Overview of verb provide The verb provide has 7 senses (first 4 from tagged texts) 1. (270) supply, provide, render, furnish -- (give something useful or necessary to; "We provided the room with an electrical heater") 2. (25) provide, supply, ply, cater -- (give what is desired or needed, especially support, food or sustenance; "The hostess provided lunch for all the guests") 3. (14) provide -- (determine (what is to happen in certain contingencies), especially by including a proviso condition or stipulation; "The will provides that each child should receive half of the money"; "The Constitution provides for the right to free speech") 4. (2) put up, provide, offer -- (mount or put up; "put up a good fight"; "offer resistance") 5. leave, allow for, allow, provide -- (make a possibility or provide opportunity for; permit to be attainable or cause to remain; "This leaves no room for improvement"; "The evidence allows only one conclusion"; "allow for mistakes"; "leave lots of time for the trip"; "This procedure provides for lots of leeway") 6. provide, bring home the bacon -- (supply means of subsistence; earn a living; "He provides for his large family by working three jobs"; "Women nowadays not only take care of the household but also bring home the bacon") 7. provide -- (take measures in preparation for; "provide for the proper care of the passengers on the cruise ship") --- WordNet end ---