title: Differential regulation of NM23-H1 under hypoxic and serum starvation conditions in metastatic cancer cells and its implication in EMT.
abstract: Multiple stresses are prevalent inside the tumor microenvironment rendering tumor growth, neighboring invasion and metastasis of the cancer cells to distant organs. NM23-H1 is the first metastasis suppressor gene identified and known to be implicated as an important regulator of stress-induced metastasis. Herein, we demonstrated that prototypical NM23-H1 expression diminished during hypoxia and serum starvation in Panc-1/MDA-MB-231 cells, but converse invasion patterns were obtained in these two diverse stresses. Supportingly, a compelling discrete difference in mRNA and protein levels of NM23-H1 was achieved in hypoxia as well as serum starvation. Knockdown of NM23-H1 activates EMT whereas the similar effects are subdued in serum starvation where NM23-H1 down-modulation prompted E-cadherin upregulation. Stable NM23-H1 expression augmented E-cadherin levels along with retardation in invadopodea formation and invasion. In hypoxia/serum starvation excess NM23-H1 effectively modulated the Twist1 promoter activity. Thus, differential regulation of NM23-H1 may corroborate/abrogate EMT depending on the nature of stress, tumor microenvironment and cellular context.
authors.affiliation: Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Reyaz Ur
authors.initials: RU
authors.lastname: Rasool
authors.affiliation: Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Debasis
authors.initials: D
authors.lastname: Nayak
authors.affiliation: Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Souneek
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Plant Biotechnology and System Biology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Vijay Lakshmi
authors.initials: VL
authors.lastname: Jamwal
authors.affiliation: Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Plant Biotechnology and System Biology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Vidushi
authors.initials: V
authors.lastname: Mahajan
authors.affiliation: Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Katoch
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Mir Mohd
authors.initials: MM
authors.lastname: Faheem
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Iqra
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Hina
authors.initials: H
authors.lastname: Amin
authors.affiliation: Plant Biotechnology and System Biology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
authors.forename: Sumit G
authors.initials: SG
authors.lastname: Gandhi
authors.affiliation: Academy of Scientific & Innovative Research (AcSIR), CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India. Electronic address: agoswami@iiim.ac.in.
authors.forename: Anindya
authors.initials: A
authors.lastname: Goswami
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D014162:Transfection; D059016:Tumor Microenvironment
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; C517938:NME1 protein, human
keywords: E-cadherin; EMT; Hypoxia; NM23-H1; Panc-1; Serum-starvation; TME