Journal Article10.1158/0008-5472.CAN-20-3328
Fam20C Regulates Bone Resorption and Breast Cancer Bone Metastasis through Osteopontin and BMP4
Hao Zuo,Dengbao Yang,Yihong Wan +2 more
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TL;DR: In this paper, it was shown that osteopontin (OPN) is a kinase that generates the majority of secreted phosphoproteins and regulates biomineralization, and its potential roles in bone resorption and breast cancer bone metastasis are unknown.
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Abstract: Fam20C is a kinase that generates the majority of secreted phosphoproteins and regulates biomineralization. However, its potential roles in bone resorption and breast cancer bone metastasis are unknown. Here we show that Fam20C in the myeloid lineage suppresses osteoclastogenesis and bone resorption, during which osteopontin (OPN) is the most abundant phosphoprotein secreted in a Fam20C-dependent manner. OPN phosphorylation by Fam20C decreased OPN secretion, and OPN neutralization reduced Fam20C-deficiency-induced osteoclast differentiation and bone metastasis. In contrast, Fam20C in breast cancer cells promoted bone metastasis by facilitating the phosphorylation and secretion of BMP4, which in turn enhanced osteoclastogenesis. Mutation of the BMP4 phosphorylation site elevated BMP4 lysosomal degradation and reduced BMP4 secretion. In breast cancer cells, BMP4 depletion or treatment with a BMP4 signaling inhibitor diminished osteoclast differentiation and bone metastasis and abolished Fam20C-mediated regulation of these processes. Collectively, this study discovers distinct roles for Fam20C in myeloid cells and breast cancer cells and highlights OPN and BMP4 as potential therapeutic targets for breast cancer bone metastasis.
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EMT mechanism in breast cancer metastasis and drug resistance: Revisiting molecular interactions and biological functions.
M. Hashemi,Hamid Zaferani Arani,Sima Orouei,Shayan Fallah,Amin Ghorbani,Maryam Khaledabadi,Amirabbas Kakavand,Alireza Tavakolpournegari,Hamidreza Saebfar,Hajar Heidari,Shokooh Salimimoghadam,Maliheh Entezari,Afshin Taheriazam,Kiavash Hushmandi +13 more
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TTN mutations predict a poor prognosis in patients with thyroid cancer
TL;DR: Wang et al. as discussed by the authors investigated the relationship between titin (TTN) gene mutations and thyroid cancer and explored the feasibility of the TTN gene as a potential prognostic indicator of THCA.
Role of osteopontin in cancer development and treatment
TL;DR: It is clarified that elevated OPN levels are observed in multiple cancer types (including colorectal, breast, lung, and liver cancer), and how OPN-macrophage interactions shape the tumor microenvironment is explored.
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The roles of m6A methylation in cervical cancer: functions, molecular mechanisms, and clinical applications
Zhonghao Mao,Bingyu Wang,Teng Zhang,Baoxia Cui +3 more
TL;DR: In the context of precision medicine, and with the advancements of genomics, proteomics, and high-throughput sequencing technologies, the application of m6A in the clinical diagnosis and treatment of CC is summarized.
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Osteopontin: A Key Multifaceted Regulator in Tumor Progression and Immunomodulation
Venketesh K. Panda,Barnalee Mishra,Angitha N. Nath,Ramesh Butti,Amit Singh Yadav,Diksha Malhotra,Sinjan Khanra,Samikshya Mahapatra,Priyanka Mishra,Biswajit Swain,Sambhunath Majhi,Kavita Kumari,N. N. V. Radharani,Gopal C. Kundu +13 more
TL;DR: This review addresses the latest advancements in the roles of splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSC enhancement, immunomodulation, metastasis, chemoresistance and metabolic reprogramming, and suggests that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.
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