Purnima K. Wagh's research while affiliated with Cincinnati Children's Hospital Medical Center and other places

... The RON receptor tyrosine kinase is expressed at low levels in epithelial cells and macrophages and is phenotypically responsible for signals to promote wound healing and the resolution of inflammation [1][2][3]. RON upregulation has significant oncogenic implications promoting cell growth, survival, migration, recruitment of pro-tumor immune cells, and suppression of anti-tumor immunity [4][5][6][7][8][9]. Hepatocyte growth factor-like (HGFL) protein, the RON ligand, ligates to two RON homodimers, leading to conformational changes that induce autophosphorylation of the tyrosine kinase (TK) domain and subsequent activation of a plethora of downstream signaling pathways [6,10,11]. ...

... It is involved in many processes, including lung development, maintenance of stem cells, cell cycle progression, and tumorigenesis. 22 Individuals with pathogenic variants in DICER1 are at increased risk of certain malignancies including PPBs, cystic nephroma, thyroid nodules, ovarian Sertoli-Leydig Cell tumor, thoracic embryonal rhabdomyosarcoma, nasal chondromesenchymal hamartoma, genitourinary sarcomas, neuroendocrine tumors, pineoblastoma, pituitary blastoma, Wilms tumor, multinodular goiter, and several other sarcomas. 7,23 Approximately 70% of all patients with PPB harbor germline mutations in DICER1 that can be identi ed with standard clinical testing. ...

... Thus, RON is an exciting target for the interrogation of recurrence biology, development of robust signatures predictive of recurrence, and is a prospective therapeutic target for the treatment or prevention of recurrent disease. The chromatin associated oncogene, DEK, is a RON-stimulated protein that promotes tumor cell proliferation [8]. Both RON and DEK have been shown to augment breast cancer stem cells, a subpopulation of treatment evading, tumor-initiating cells implicated in cancer recurrence [9,10]. ...

... Both RON and DEK have been shown to augment breast cancer stem cells, a subpopulation of treatment evading, tumor-initiating cells implicated in cancer recurrence [9,10]. Mechanistically, RON and DEK promote β-catenin activation through independent mechanisms that synergize to support breast cancer stem cell self-renewal and breast cancer metastasis in preclinical models [8][9][10][11][12][13]. ...

... In addition, aberrant activation of the receptor has been described in many solid tumors. These include pancreas, lung, liver, breast, colon, prostate, bladder, and ovarian cancers, as well as AML and Burkitt lymphoma [13][14][15][16][17][18][19][20][21][22][23][24][25]. RON activation contributes to tumor progression and metastasis by promoting cell proliferation, motility, and inhibiting apoptosis. ...

... Both RON and DEK have been shown to augment breast cancer stem cells, a subpopulation of treatment evading, tumor-initiating cells implicated in cancer recurrence [9,10]. Mechanistically, RON and DEK promote β-catenin activation through independent mechanisms that synergize to support breast cancer stem cell self-renewal and breast cancer metastasis in preclinical models [8][9][10][11][12][13]. ...

... The chromatin associated oncogene, DEK, is a RON-stimulated protein that promotes tumor cell proliferation [8]. Both RON and DEK have been shown to augment breast cancer stem cells, a subpopulation of treatment evading, tumor-initiating cells implicated in cancer recurrence [9,10]. Mechanistically, RON and DEK promote β-catenin activation through independent mechanisms that synergize to support breast cancer stem cell self-renewal and breast cancer metastasis in preclinical models [8][9][10][11][12][13]. ...

... Tumoral RON expression correlates with increased BCa progression, metastasis, and poor prognosis independent of molecular subtype [8,10,27,28]. RON activation leads to downstream activation of several signaling cascades that promote pleiotropic functions, including cell proliferation, invasion, angiogenesis, therapeutic resistance, and stemness [8,10,27,29,30]. Several gain and lossof-function mouse models have established RON upregulation in epithelial cells as a key driver of mammary tumorigenesis [31,32] while global RON or HGFL knockout in BCa [27,33] abrogates tumorigenesis. ...

... 3.5. USP39 is positively correlated to CHK2 in clinical lung cancer samples CHK2 has been identified as a tumor suppressor, which is mutated or depleted in various cancers, including breast, colon, bladder, ovary and prostate carcinomas, albeit at low frequencies [49][50][51][52]. Besides mutated in cancer, low level of CHK2 was also observed in lung cancers, which contributes to chemo-radiation resistance [53][54][55]. ...

... LAMP2a is manifested to be activated by various external stressors in TME, such as hypoxia and androgen deprivation [68]. e RON receptor (MST1R), a Met tyrosine kinase receptor family member, exists preferentially in prostate epithelial cells and macrophages [69,70]. Prior work demonstrated macrophage-intrinsic RON as a negative regulator of macrophage activation. ...