Metastasis　is　the　leading　cause　of　cancer-related　deaths　and　poses　a　treatment　challenge.　Although　studies　have　shown　the　importance　of　epithelial-mesenchymal　transition　(EMT)　and　metabolic　reprogramming　during　cancer　metastasis,　the　link　between　EMT　and　metabolic　reprogramming,　as　well　as　the　underlying　molecular　mechanisms　by　which　both　mediate　cancer　cell　invasion　and　metastasis　have　not　been　elucidated.　Here,　we　observed　that　interactions　between　platelets　and　cancer　cells　promote　the　secretion　of　TGF-beta,　thereby　initiating　EMT,　promoting　the　invasion,　and　altering　the　metastatic　and　metabolic　potential　of　colon　cancer　cells.　TGF-beta　activates　the　AKT　signaling　pathway　to　enhance　HK1　and　HK2　expression　in　cancer　cells,　leading　to　increased　glucose　consumption,　ATP　production,　and　precise　modulation　of　cell　cycle　distribution.　In　an　energy-deficient　model　induced　by　oxidative　phosphorylation　(OXPHOS)　inhibition　with　oligomycin　A,　TGF-beta-induced　highly　metastatic　HCT116　(H-HCT116)　cells　adapt　by　upregulating　HK　expression　and　glycolytic　metabolism,　while　concurrently　decreasing　cell　proliferation　to　conserve　energy　for　survival.　Mechanistically,　H-HCT116　cells　regulate　cell　division　rates　by　downregulating　CDK2,　CDK4,　and　Cyclin　D1　protein　expression　and　upregulating　p21　expression.　Furthermore,　H-HCT116　cells　display　enhanced　motility,　which　is　linked　to　increased　mitochondrial　metabolic　activity.　These　findings　indicated　that　cancer　cells-platelets　interaction　secreted　TGF-beta　activates　cancer　metastasis　potential　by　inducing　metabolic　reprogramming　and　bioenergetic　adaptation.　The　present　study　provides　new　insights　into　the　adaptive　strategies　of　highly　metastatic　cancer　cells　under　adverse　conditions　and　indicates　that　targeting　glycolysis　and　metabolic　reprogramming　could　serve　as　a　viable　approach　to　prevent　cancer　metastasis.